Nuclear pore and nucleocytoplasmic transport impairment in oxidative stress-induced neurodegeneration: relevance to molecular mechanisms in Pathogenesis of Parkinson’s and other related neurodegenerative diseases

  • Cook A, Bono F, Jinek M, Conti E. Structural biology of nucleocytoplasmic transport. Annu Rev Biochem. 2007;76:647–71.

    Article  PubMed  Google Scholar 

  • Doye V, Hurt E. From nucleoporins to nuclear pore complexes. Curr Opin Cell Biol. 1997;9(3):401–11.

    Article  PubMed  Google Scholar 

  • Ptak C, Aitchison JD, Wozniak RW. The multifunctional nuclear pore complex: a platform for controlling gene expression. Curr Opin Cell Biol. 2014;28:46–53.

    Article  PubMed  Google Scholar 

  • Ribbeck K, Görlich D. The permeability barrier of nuclear pore complexes appears to operate via hydrophobic exclusion. EMBO J. 2002;21(11):2664–71.

    Article  PubMed  PubMed Central  Google Scholar 

  • Toyama B, Arrojo e Drigo R, Lev-Ram V, Ramachandra R, Deerinck T, Lechene C, Ellisman M, Hetzer M. Visualization of long-lived proteins reveals age mosaicism within nuclei of postmitotic cells. J Cell Biol. 2018;218:jcb201809123.

    Google Scholar 

  • Hetzer MW. The role of the nuclear pore complex in aging of post-mitotic cells. Aging. 2010;2(2):74–5.

    Article  PubMed  PubMed Central  Google Scholar 

  • Savas JN, Toyama BH, Xu T, Yates JR 3rd, Hetzer MW. Extremely long-lived nuclear pore proteins in the rat brain. Science. 2012;335(6071):942.

    Article  PubMed  PubMed Central  Google Scholar 

  • Spead O, Zaepfel BL, Rothstein JD. Nuclear Pore Dysfunction in Neurodegeneration. Neurotherapeutics. 2022;19(4):1050–60.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cristi AC, Rapuri S, Coyne AN. Nuclear pore complex and nucleocytoplasmic transport disruption in neurodegeneration. FEBS Lett. 2023.

  • Patel V, Chu C. Nuclear transport, oxidative stress, and neurodegeneration. Int J Clin Exp Pathol. 2011;4:215–29.

    PubMed  PubMed Central  Google Scholar 

  • Devos D, Dokudovskaya S, Williams R, Alber F, Eswar N, Chait BT, Rout MP, Sali A. Simple Fold composition and modular architecture of the nuclear pore complex. Proc Natl Acad Sci U S A. 2006;103(7):2172–7.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lin DH, Hoelz A. The structure of the Nuclear Pore Complex (an update). Annu Rev Biochem. 2019;88:725–83.

    Article  PubMed  PubMed Central  Google Scholar 

  • von Appen A, Beck M. Structure determination of the Nuclear Pore Complex with three-dimensional Cryo electron Microscopy. J Mol Biol. 2016;428(10 Pt A):2001–10.

    Article  Google Scholar 

  • Hakhverdyan Z, Molloy KR, Keegan S, Herricks T, Lepore DM, Munson M, Subbotin RI, Fenyö D, Aitchison JD, Fernandez-Martinez J, et al. Dissecting the Structural dynamics of the Nuclear Pore Complex. Mol Cell. 2021;81(1):153–e165157.

    Article  PubMed  Google Scholar 

  • Denning DP, Patel SS, Uversky V, Fink AL, Rexach M. Disorder in the nuclear pore complex: the FG repeat regions of nucleoporins are natively unfolded. Proc Natl Acad Sci U S A. 2003;100(5):2450–5.

    Article  PubMed  PubMed Central  Google Scholar 

  • Strawn LA, Shen T, Shulga N, Goldfarb DS, Wente SR. Minimal nuclear pore complexes define FG repeat domains essential for transport. Nat Cell Biol. 2004;6(3):197–206.

    Article  PubMed  Google Scholar 

  • Dekker M, Van der Giessen E, Onck PR. Phase separation of intrinsically disordered FG-Nups is driven by highly dynamic FG motifs. Proceedings of the National Academy of Sciences. 2023, 120(25):e2221804120.

  • Khalil B, Linsenmeier M, Smith CL, Shorter J, Rossoll W. Nuclear-import receptors as gatekeepers of pathological phase transitions in ALS/FTD. Mol Neurodegener. 2024;19(1):8.

    Article  PubMed  PubMed Central  Google Scholar 

  • Beck M, Hurt E. The nuclear pore complex: understanding its function through structural insight. Nat Rev Mol Cell Biol. 2017;18(2):73–89.

    Article  PubMed  Google Scholar 

  • Bui Khanh H, von Appen A, DiGuilio Amanda L, Ori A, Sparks L, Mackmull M-T, Bock T, Hagen W, Andrés-Pons A, Glavy Joseph S, et al. Integrated Structural Analysis of the Human Nuclear Pore Complex Scaffold. Cell. 2013;155(6):1233–43.

    Article  PubMed  Google Scholar 

  • Kampmann M, Blobel G. Three-dimensional structure and flexibility of a membrane-coating module of the nuclear pore complex. Nat Struct Mol Biol. 2009;16(7):782–8.

    Article  PubMed  PubMed Central  Google Scholar 

  • Boehmer T, Enninga J, Dales S, Blobel G, Zhong H. Depletion of a single nucleoporin, Nup107, prevents the assembly of a subset of nucleoporins into the nuclear pore complex. Proc Natl Acad Sci. 2003;100(3):981–5.

    Article  PubMed  PubMed Central  Google Scholar 

  • Walther TC, Alves A, Pickersgill H, Loïodice I, Hetzer M, Galy V, Hülsmann BB, Köcher T, Wilm M, Allen T, et al. The conserved Nup107-160 complex is critical for nuclear pore complex assembly. Cell. 2003;113(2):195–206.

    Article  PubMed  Google Scholar 

  • Fernandez-Martinez J, Rout MP. One Ring to rule them all? Structural and functional diversity in the Nuclear Pore Complex. Trends Biochem Sci. 2021;46(7):595–607.

    Article  PubMed  PubMed Central  Google Scholar 

  • Eisenhardt N, Redolfi J, Antonin W. Interaction of Nup53 with Ndc1 and Nup155 is required for nuclear pore complex assembly. J Cell Sci. 2014;127(Pt 4):908–21.

    PubMed  Google Scholar 

  • Mosalaganti S, Obarska-Kosinska A, Siggel M, Taniguchi R, Turoňová B, Zimmerli CE, Buczak K, Schmidt FH, Margiotta E, Mackmull M-T, et al. AI-based structure prediction empowers integrative structural analysis of human nuclear pores. Science. 2022;376(6598):eabm9506.

    Article  PubMed  Google Scholar 

  • Sakuma S, Raices M, Borlido J, Guglielmi V, Zhu EYS, D’Angelo MA. Inhibition of nuclear pore complex formation selectively induces Cancer Cell Death. Cancer Discov. 2021;11(1):176–93.

    Article  PubMed  Google Scholar 

  • Funakoshi T, Maeshima K, Yahata K, Sugano S, Imamoto F, Imamoto N. Two distinct human POM121 genes: requirement for the formation of nuclear pore complexes. FEBS Lett. 2007;581(25):4910–6.

    Article  PubMed  Google Scholar 

  • Bindra D, Mishra RK. In pursuit of distinctiveness: transmembrane nucleoporins and their Disease associations. Front Oncol. 2021;11:784319.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mansfeld J, Güttinger S, Hawryluk-Gara LA, Panté N, Mall M, Galy V, Haselmann U, Mühlhäusser P, Wozniak RW, Mattaj IW, et al. The conserved transmembrane nucleoporin NDC1 is required for nuclear pore complex assembly in vertebrate cells. Mol Cell. 2006;22(1):93–103.

    Article  PubMed  Google Scholar 

  • Kind B, Koehler K, Lorenz M, Huebner A. The nuclear pore complex protein ALADIN is anchored via NDC1 but not via POM121 and GP210 in the nuclear envelope. Biochem Biophys Res Commun. 2009;390(2):205–10.

    Article  PubMed  Google Scholar 

  • Funakoshi T, Clever M, Watanabe A, Imamoto N. Localization of Pom121 to the inner nuclear membrane is required for an early step of interphase nuclear pore complex assembly. Mol Biol Cell. 2011;22(7):1058–69.

    Article  PubMed  PubMed Central  Google Scholar 

  • Talamas JA, Hetzer MW. POM121 and Sun1 play a role in early steps of interphase NPC assembly. J Cell Biol. 2011;194(1):27–37.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mitchell JM, Mansfeld J, Capitanio J, Kutay U, Wozniak RW. Pom121 links two essential subcomplexes of the nuclear pore complex core to the membrane. J Cell Biol. 2010;191(3):505–21.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hu T, Guan T, Gerace L. Molecular and functional characterization of the p62 complex, an assembly of nuclear pore complex glycoproteins. J Cell Biol. 1996;134(3):589–601.

    Article  PubMed  Google Scholar 

  • Chug H, Trakhanov S, Hülsmann BB, Pleiner T, Görlich D. Crystal structure of the metazoan Nup62•Nup58•Nup54 nucleoporin complex. Science. 2015;350(6256):106–10.

    Article  PubMed  Google Scholar 

  • Hampoelz B, Andres-Pons A, Kastritis P, Beck M. Structure and assembly of the Nuclear Pore Complex. Annual Rev Biophys. 2019;48(1):515–36.

    Article  Google Scholar 

  • Finlay DR, Meier E, Bradley P, Horecka J, Forbes DJ. A complex of nuclear pore proteins required for pore function. J Cell Biol. 1991;114(1):169–83.

    Article  PubMed  Google Scholar 

  • Percipalle P, Clarkson WD, Kent HM, Rhodes D, Stewart M. Molecular interactions between the importin α/β heterodimer and proteins involved in vertebrate nuclear protein import11Edited by J. Karn. J Mol Biol. 1997;266(4):722–32.

    Article  PubMed  Google Scholar 

  • Macara IG. Transport into and out of the nucleus. Microbiol Mol Biol Rev. 2001;65(4):570–94. table of contents.

    Article  PubMed  PubMed Central  Google Scholar 

  • Terry LJ, Wente SR. Flexible gates: dynamic topologies and functions for FG nucleoporins in nucleocytoplasmic transport. Eukaryot Cell. 2009;8(12):1814–27.

    Article  PubMed  PubMed Central  Google Scholar 

  • Solmaz SR, Chauhan R, Blobel G, Melčák I. Molecular architecture of the transport channel of the nuclear pore complex. Cell. 2011;147(3):590–602.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kabachinski G, Schwartz TU. The nuclear pore complex–structure and function at a glance. J Cell Sci. 2015;128(3):423–9.

    Article  PubMed  PubMed Central  Google Scholar 

  • Frey S, Richter RP, Görlich D. FG-Rich repeats of Nuclear Pore proteins Form a three-Dimensional Meshwork with Hydrogel-Like Properties. Science. 2006;314(5800):815–7.

    Article  PubMed  Google Scholar 

  • Hülsmann Bastian B, Labokha Aksana A, Görlich D. The permeability of Reconstituted Nuclear pores provides direct evidence for the selective phase model. Cell. 2012;150(4):738–51.

    Article  PubMed  Google Scholar 

  • Ng SC, Biswas A, Huyton T, Schünemann J, Reber S, Görlich D. Barrier properties of Nup98 FG phases ruled by FG motif identity and inter-FG spacer length. Nat Commun. 2023;14(1):747.

    Article  PubMed  PubMed Central  Google Scholar 

  • Petrovic S, Samanta D, Perriches T, Bley CJ, Thierbach K, Brown B, Nie S, Mobbs GW, Stevens TA, Liu X, et al. Architecture of the linker-scaffold in the nuclear pore. Science. 2022;376(6598):eabm9798.

    Article  PubMed  PubMed Central  Google Scholar 

  • Oka M, Asally M, Yasuda Y, Ogawa Y, Tachibana T, Yoneda Y. The mobile FG nucleoporin Nup98 is a cofactor for Crm1-dependent protein export. Mol Biol Cell. 2010;21(11):1885–96.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bangs P, Burke B, Powers C, Craig R, Purohit A, Doxsey S. Functional analysis of Tpr: identification of nuclear pore complex association and nuclear localization domains and a role in mRNA export. J Cell Biol. 1998;143(7):1801–12.

    Article  PubMed  PubMed Central  Google Scholar 

  • Guan T, Kehlenbach RH, Schirmer EC, Kehlenbach A, Fan F, Clurman BE, Arnheim N, Gerace L. Nup50, a nucleoplasmically oriented nucleoporin with a role in nuclear protein export. Mol Cell Biol. 2000;20(15):5619–30.

    Article  PubMed  PubMed Central  Google Scholar 

  • Panté N, Aebi U. Molecular dissection of the Nuclear Pore Complex. Crit Rev Biochem Mol Biol. 1996;31(2):153–99.

    Article  PubMed  Google Scholar 

  • Hoelz A, Debler EW, Blobel G. The structure of the nuclear pore complex. Annu Rev Biochem. 2011;80:613–43.

    Article  PubMed  Google Scholar 

  • Krull S, Thyberg J, Björkroth B, Rackwitz HR, Cordes VC. Nucleoporins as components of the nuclear pore complex core structure and tpr as the architectural element of the nuclear basket. Mol Biol Cell. 2004;15(9):4261–77.

    Article  PubMed  PubMed Central  Google Scholar 

  • Tingey M, Li Y, Yu W, Young A, Yang W. Spelling out the roles of individual nucleoporins in nuclear export of mRNA. Nucleus (Calcutta). 2022;13(1):172–95.

    Article  Google Scholar 

  • David-Watine B. Silencing nuclear pore protein Tpr elicits a senescent-like phenotype in cancer cells. PLoS ONE. 2011;6(7):e22423.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhao CL, Mahboobi SH, Moussavi-Baygi R, Mofrad MR. The interaction of CRM1 and the nuclear pore protein Tpr. PLoS ONE. 2014;9(4):e93709.

    Article  PubMed  PubMed Central  Google Scholar 

  • McCloskey A, Ibarra A, Hetzer MW. Tpr regulates the total number of nuclear pore complexes per cell nucleus. Genes Dev. 2018;32(19–20):1321–31.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lindsay ME, Plafker K, Smith AE, Clurman BE, Macara IG. Npap60/Nup50 is a tri-stable switch that stimulates importin-alpha:beta-mediated nuclear protein import. Cell. 2002;110(3):349–60.

    Article  PubMed  Google Scholar 

  • Makise M, Mackay DR, Elgort S, Shankaran SS, Adam SA, Ullman KS. The Nup153-Nup50 protein interface and its role in nuclear import. J Biol Chem. 2012;287(46):38515–22.

    Article  PubMed  PubMed Central  Google Scholar 

  • Duheron V, Chatel G, Sauder U, Oliveri V, Fahrenkrog B. Structural characterization of altered nucleoporin Nup153 expression in human cells by thin-section electron microscopy. Nucleus (Calcutta). 2014;5(6):601–12.

    Article  Google Scholar 

  • Li P, Noegel AA. Inner nuclear envelope protein SUN1 plays a prominent role in mammalian mRNA export. Nucleic Acids Res. 2015;43(20):9874–88.

    PubMed  PubMed Central  Google Scholar 

  • Walther TC, Fornerod M, Pickersgill H, Goldberg M, Allen TD, Mattaj IW. The nucleoporin Nup153 is required for nuclear pore basket formation, nuclear pore complex anchoring and import of a subset of nuclear proteins. EMBO J. 2001;20(20):5703–14.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lenz-Böhme B, Wismar J, Fuchs S, Reifegerste R, Buchner E, Betz H, Schmitt B. Insertional mutation of the Drosophila nuclear lamin Dm0 gene results in defective nuclear envelopes, clustering of nuclear pore complexes, and accumulation of annulate lamellae. J Cell Biol. 1997;137(5):1001–16.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bley CJ, Nie S, Mobbs GW, Petrovic S, Gres AT, Liu X, Mukherjee S, Harvey S, Huber FM, Lin DH, et al. Architecture of the cytoplasmic face of the nuclear pore. Science. 2022;376(6598):eabm9129.

    Article  PubMed  PubMed Central  Google Scholar 

  • Werner A, Flotho A, Melchior F. The RanBP2/RanGAP1SUMO1/Ubc9 complex is a multisubunit SUMO E3 ligase. Mol Cell. 2012;46(3):287–98.

    Article  PubMed  Google Scholar 

  • Mahadevan K, Zhang H, Akef A, Cui XA, Gueroussov S, Cenik C, Roth FP, Palazzo AF. RanBP2/Nup358 potentiates the translation of a subset of mRNAs encoding secretory proteins. PLoS Biol. 2013;11(4):e1001545.

    Article  PubMed  PubMed Central  Google Scholar 

  • Fornerod M, van Deursen J, van Baal S, Reynolds A, Davis D, Murti KG, Fransen J, Grosveld G. The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88. EMBO J. 1997;16(4):807–16.

    Article  PubMed  PubMed Central  Google Scholar 

  • Katahira J, Strässer K, Podtelejnikov A, Mann M, Jung JU, Hurt E. The Mex67p-mediated nuclear mRNA export pathway is conserved from yeast to human. EMBO J. 1999;18(9):2593–609.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kendirgi F, Rexer DJ, Alcázar-Román AR, Onishko HM, Wente SR. Interaction between the shuttling mRNA export factor Gle1 and the nucleoporin hCG1: a conserved mechanism in the export of Hsp70 mRNA. Mol Biol Cell. 2005;16(9):4304–15.

    Article  PubMed  PubMed Central  Google Scholar 

  • von Moeller H, Basquin C, Conti E. The mRNA export protein DBP5 binds RNA and the cytoplasmic nucleoporin NUP214 in a mutually exclusive manner. Nat Struct Mol Biol. 2009;16(3):247–54.

    Article  Google Scholar 

  • Alcázar-Román AR, Tran EJ, Guo S, Wente SR. Inositol hexakisphosphate and Gle1 activate the DEAD-box protein Dbp5 for nuclear mRNA export. Nat Cell Biol. 2006;8(7):711–6.

    Article  PubMed  Google Scholar 

  • Ren Y, Seo H-S, Blobel G, Hoelz A. Structural and functional analysis of the interaction between the nucleoporin Nup98 and the mRNA export factor Rae1. Proc Nat Acad Sci. 2010, 107(23):10406–10411.

  • Rajoo S, Vallotton P, Onischenko E, Weis K. Stoichiometry and compositional plasticity of the yeast nuclear pore complex revealed by quantitative fluorescence microscopy. Proc Natl Acad Sci. 2018;115(17):E3969–77.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim SJ, Fernandez-Martinez J, Nudelman I, Shi Y, Zhang W, Raveh B, Herricks T, Slaughter BD, Hogan JA, Upla P, et al. Integrative structure and functional anatomy of a nuclear pore complex. Nature. 2018;555(7697):475–82.

    Article  PubMed  PubMed Central  Google Scholar 

  • Nuclear Pore Complexes: Global Conservation and Local Variation. Curr Biol. 2018, 28(11):R674-R677.

  • Tran EJ, Wente SR. Dynamic nuclear pore complexes: life on the Edge. Cell. 2006;125(6):1041–53.

    Article  PubMed  Google Scholar 

  • Beck M, Förster F, Ecke M, Plitzko JM, Melchior F, Gerisch G, Baumeister W, Medalia O. Nuclear Pore Complex structure and Dynamics revealed by Cryoelectron Tomography. Science. 2004;306(5700):1387–90.

    Article  PubMed  Google Scholar 

  • Sakiyama Y, Mazur A, Kapinos LE, Lim RYH. Spatiotemporal dynamics of the nuclear pore complex transport barrier resolved by high-speed atomic force microscopy. Nat Nanotechnol. 2016;11(8):719–23.

    Article  PubMed  Google Scholar 

  • D’Angelo MA, Raices M, Panowski SH, Hetzer MW. Age-dependent deterioration of nuclear pore complexes causes a loss of nuclear integrity in postmitotic cells. Cell. 2009;136(2):284–95.

    Article  PubMed  PubMed Central  Google Scholar 

  • Toyama Brandon H, Savas Jeffrey N, Park Sung K, Harris Michael S, Ingolia Nicholas T, Yates John R III. Hetzer Martin W: identification of long-lived proteins reveals exceptional Stability of essential Cellular structures. Cell. 2013;154(5):971–82.

    Article  PubMed  PubMed Central  Google Scholar 

  • Rabut G, Doye V, Ellenberg J. Mapping the dynamic organization of the nuclear pore complex inside single living cells. Nat Cell Biol. 2004;6(11):1114–21.

    Article  PubMed  Google Scholar 

  • Timney BL, Raveh B, Mironska R, Trivedi JM, Kim SJ, Russel D, Wente SR, Sali A, Rout MP. Simple rules for passive diffusion through the nuclear pore complex. J Cell Biol. 2016;215(1):57–76.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cole CN, Hammell CM. Nucleocytoplasmic transport: driving and directing transport. Curr Biol. 1998;8(11):R368–72.

    Article  PubMed  Google Scholar 

  • Wing CE, Fung HYJ, Chook YM. Karyopherin-mediated nucleocytoplasmic transport. Nat Rev Mol Cell Biol. 2022;23(5):307–28.

    Article  PubMed  PubMed Central  Google Scholar 

  • Izaurralde E, Kutay U, von Kobbe C, Mattaj IW, Görlich D. The asymmetric distribution of the constituents of the ran system is essential for transport into and out of the nucleus. EMBO J. 1997;16(21):6535–47.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kalita J, Kapinos LE, Lim RYH. On the asymmetric partitioning of nucleocytoplasmic transport – recent insights and open questions. J Cell Sci 2021, 134(7).

    Article  PubMed  Google Scholar 

  • Stewart M. Molecular mechanism of the nuclear protein import cycle. Nat Rev Mol Cell Biol. 2007;8(3):195–208.

    Article  PubMed  Google Scholar 

  • Lui K, Huang Y. RanGTPase: a Key Regulator of nucleocytoplasmic trafficking. Mol Cell Pharmacol. 2009;1(3):148–56.

    Article  PubMed  PubMed Central  Google Scholar 

  • Köhler A, Hurt E. Exporting RNA from the nucleus to the cytoplasm. Nat Rev Mol Cell Biol. 2007;8(10):761–73.

    Article  PubMed  Google Scholar 

  • Carmody SR, Wente SR. mRNA nuclear export at a glance. J Cell Sci. 2009;122(Pt 12):1933–7.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kalverda B, Pickersgill H, Shloma VV, Fornerod M. Nucleoporins directly stimulate expression of developmental and cell-cycle genes inside the nucleoplasm. Cell. 2010;140(3):360–71.

    Article  PubMed  Google Scholar 

  • Capelson M, Liang Y, Schulte R, Mair W, Wagner U, Hetzer MW. Chromatin-bound nuclear pore components regulate gene expression in higher eukaryotes. Cell. 2010;140(3):372–83.

    Article  PubMed  PubMed Central  Google Scholar 

  • Menon BB, Sarma NJ, Pasula S, Deminoff SJ, Willis KA, Barbara KE, Andrews B, Santangelo GM. Reverse recruitment: the Nup84 nuclear pore subcomplex mediates Rap1/Gcr1/Gcr2 transcriptional activation. Proc Natl Acad Sci U S A. 2005;102(16):5749–54.

    Article  PubMed  PubMed Central  Google Scholar 

  • D’Angelo MA. Nuclear pore complexes as hubs for gene regulation. Nucleus (Calcutta). 2018;9(1):142–8.

    Article  Google Scholar 

  • Ibarra A, Benner C, Tyagi S, Cool J, Hetzer MW. Nucleoporin-mediated regulation of cell identity genes. Genes Dev. 2016;30(20):2253–8.

    Article  PubMed  PubMed Central  Google Scholar 

  • Jacinto FV, Benner C, Hetzer MW. The nucleoporin Nup153 regulates embryonic stem cell pluripotency through gene silencing. Genes Dev. 2015;29(12):1224–38.

    Article  PubMed  PubMed Central  Google Scholar 

  • Vaquerizas JM, Suyama R, Kind J, Miura K, Luscombe NM, Akhtar A. Nuclear pore proteins nup153 and megator define transcriptionally active regions in the Drosophila genome. PLoS Genet. 2010;6(2):e1000846.

    Article  PubMed  PubMed Central  Google Scholar 

  • Capelson M. You are who your friends are—nuclear pore proteins as components of chromatin-binding complexes. FEBS Lett. 2023.

  • Kuhn TM, Capelson M. Nuclear pore proteins in regulation of chromatin state. Cells 2019, 8(11).

    Article  PubMed  PubMed Central  Google Scholar 

  • Colussi C, Grassi C. Epigenetic regulation of neural stem cells: the emerging role of Nucleoporins. Stem Cells. 2021;39(12):1601–14.

    Article  PubMed  Google Scholar 

  • Simon M-N, Dubrana K, Palancade B. On the edge: how nuclear pore complexes rule genome stability. Curr Opin Genet Dev. 2024;84:102150.

    Article  PubMed  Google Scholar 

  • Mackay DR, Howa AC, Werner TL, Ullman KS. Nup153 and Nup50 promote recruitment of 53BP1 to DNA repair foci by antagonizing BRCA1-dependent events. J Cell Sci. 2017;130(19):3347–59.

    Article  PubMed  Google Scholar 

  • Moudry P, Lukas C, Macurek L, Neumann B, Heriche JK, Pepperkok R, Ellenberg J, Hodny Z, Lukas J, Bartek J. Nucleoporin NUP153 guards genome integrity by promoting nuclear import of 53BP1. Cell Death Differ. 2012;19(5):798–807.

    Article  PubMed  Google Scholar 

  • de Miranda BR, Greenamyre JT. CHAPTER 1 etiology and Pathogenesis of Parkinson’s Disease. Oxidative stress and Redox Signalling in Parkinson’s Disease. The Royal Society of Chemistry; 2017. pp. 1–26.

    Google Scholar 

  • Kouli A, Torsney KM, Kuan W-L. Parkinson’s Disease: Etiology, Neuropathology, and Pathogenesis. 2018.

  • Xia Q, Liao L, Cheng D, Duong DM, Gearing M, Lah JJ, Levey AI, Peng J. Proteomic identification of novel proteins associated with Lewy bodies. Front Biosci. 2008;13:3850–6.

    Article  PubMed  PubMed Central  Google Scholar 

  • Postuma RB, Aarsland D, Barone P, Burn DJ, Hawkes CH, Oertel W, Ziemssen T. Identifying prodromal Parkinson’s disease: pre-motor disorders in Parkinson’s disease. Mov Disord. 2012;27(5):617–26.

    Article  PubMed  Google Scholar 

  • Funayama M, Nishioka K, Li Y, Hattori N. Molecular genetics of Parkinson’s disease: contributions and global trends. J Hum Genet. 2023;68(3):125–30.

    Article  PubMed  Google Scholar 

  • Ball N, Teo WP, Chandra S, Chapman J. Parkinson’s Disease and the Environment. Front Neurol. 2019;10:218.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pouchieu C, Piel C, Carles C, Gruber A, Helmer C, Tual S, Marcotullio E, Lebailly P, Baldi I. Pesticide use in agriculture and Parkinson’s disease in the AGRICAN cohort study. Int J Epidemiol. 2018;47(1):299–310.

    Article  PubMed  Google Scholar 

  • Narayan S, Liew Z, Bronstein JM, Ritz B. Occupational pesticide use and Parkinson’s disease in the Parkinson Environment Gene (PEG) study. Environ Int. 2017;107:266–73.

    Article  PubMed  PubMed Central  Google Scholar 

  • Vellingiri B, Suriyanarayanan A, Abraham KS, Venkatesan D, Iyer M, Raj N, Gopalakrishnan AV. Influence of heavy metals in Parkinson’s disease: an overview. J Neurol. 2022;269(11):5798–811.

    Article  PubMed  Google Scholar 

  • Hindle JV. Ageing, neurodegeneration and Parkinson’s disease. Age Ageing. 2010;39(2):156–61.

    Article  PubMed  Google Scholar 

  • Willis AW, Roberts E, Beck JC, Fiske B, Ross W, Savica R, Van Den Eeden SK, Tanner CM, Marras C, Alcalay R, et al. Incidence of Parkinson disease in North America. Npj Parkinson’s Disease. 2022;8(1):170.

    Article  PubMed  PubMed Central  Google Scholar 

  • Schapira AHV, Cooper JM, Dexter D, Jenner P, Clark JB, Marsden CD. MITOCHONDRIAL COMPLEX I DEFICIENCY IN PARKINSON’S DISEASE. Lancet. 1989;333(8649):1269.

    Article  Google Scholar 

  • Mizuno Y, Ohta S, Tanaka M, Takamiya S, Suzuki K, Sato T, Oya H, Ozawa T, Kagawa Y. Deficiencies in complex I subunits of the respiratory chain in Parkinson’s disease. Biochem Biophys Res Commun. 1989;163(3):1450–5.

    Article  PubMed  Google Scholar 

  • Keeney PM, Xie J, Capaldi RA, Bennett JP Jr. Parkinson’s disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled. J Neurosci. 2006;26(19):5256–64.

    Article  PubMed  PubMed Central  Google Scholar 

  • Toomey CE, Heywood WE, Evans JR, Lachica J, Pressey SN, Foti SC, Al Shahrani M, D’Sa K, Hargreaves IP, Heales S, et al. Mitochondrial dysfunction is a key pathological driver of early stage Parkinson’s. Acta Neuropathol Commun. 2022;10(1):134.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen C, McDonald D, Blain A, Mossman E, Atkin K, Marusich MF, Capaldi R, Bone L, Smith A, Filby A, et al. Parkinson’s disease neurons exhibit alterations in mitochondrial quality control proteins. Npj Parkinson’s Disease. 2023;9(1):120.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pacelli C, Giguère N, Bourque MJ, Lévesque M, Slack RS, Trudeau L. Elevated mitochondrial bioenergetics and axonal arborization size are key contributors to the vulnerability of dopamine neurons. Curr Biol. 2015;25(18):2349–60.

    Article  PubMed  Google Scholar 

  • Haddad D, Nakamura K. Understanding the susceptibility of dopamine neurons to mitochondrial stressors in Parkinson’s disease. FEBS Lett. 2015;589(24 Pt A):3702–13.

    Article  PubMed  PubMed Central  Google Scholar 

  • Surmeier DJ. Determinants of dopaminergic neuron loss in Parkinson’s disease. Febs j. 2018;285(19):3657–68.

    Article  PubMed  PubMed Central  Google Scholar 

  • Meiser J, Weindl D, Hiller K. Complexity of dopamine metabolism. Cell Communication Signal. 2013;11(1):34.

    Article  Google Scholar 

  • Helley MP, Pinnell J, Sportelli C, Tieu K. Mitochondria: a common target for genetic mutations and environmental toxicants in Parkinson’s Disease. Front Genet. 2017;8:177.

    Article  PubMed  PubMed Central  Google Scholar 

  • Li W, Fu Y, Halliday GM, Sue CM. PARK genes Link mitochondrial dysfunction and alpha-Synuclein Pathology in sporadic Parkinson’s Disease. Front Cell Dev Biol. 2021;9:612476.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mitochondrial Dysfunction in Dopaminergic Neurons Derived from Patients with LRRK2-and SNCA-Associated Genetic Forms of Parkinson’s Disease. Curr Issues Mol Biol 2023, 45(10):8395–8411.

  • Park J-S, Davis RL, Sue CM. Mitochondrial dysfunction in Parkinson’s Disease: new mechanistic insights and therapeutic perspectives. Curr Neurol Neurosci Rep. 2018;18(5):21–21.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, Kachergus J, Hulihan M, Uitti RJ, Calne DB, et al. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron. 2004;44(4):601–7.

    Article  PubMed  Google Scholar 

  • Singh A, Zhi L, Zhang H. LRRK2 and mitochondria: recent advances and current views. Brain Res. 2019;1702:96–104.

    Article  PubMed  Google Scholar 

  • Pickrell AM, Youle RJ. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron. 2015;85(2):257–73.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ge P, Dawson VL, Dawson TM. PINK1 and Parkin mitochondrial quality control: a source of regional vulnerability in Parkinson’s disease. Mol Neurodegener. 2020;15(1):20.

    Article  PubMed  PubMed Central  Google Scholar 

  • Davis GC, Williams AC, Markey SP, Ebert MH, Caine ED, Reichert CM, Kopin IJ. Chronic parkinsonism secondary to intravenous injection of meperidine analogues. Psychiatry Res. 1979;1(3):249–54.

    Article  PubMed  Google Scholar 

  • Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science. 1983;219(4587):979–80.

    Article  PubMed  Google Scholar 

  • Spivey A. Rotenone and paraquat linked to Parkinson’s disease: human exposure study supports years of animal studies. Environ Health Perspect. 2011;119(6):A259–259.

    Article  PubMed  PubMed Central  Google Scholar 

  • Tanner CM, Kamel F, Ross GW, Hoppin JA, Goldman SM, Korell M, Marras C, Bhudhikanok GS, Kasten M, Chade AR, et al. Rotenone, paraquat, and Parkinson’s disease. Environ Health Perspect. 2011;119(6):866–72.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pezzoli G, Cereda E. Exposure to pesticides or solvents and risk of Parkinson disease. Neurology. 2013;80(22):2035–41.

    Article  PubMed  Google Scholar 

  • Huang M, Bargues-Carot A, Riaz Z, Wickham H, Zenitsky G, Jin H, Anantharam V, Kanthasamy A, Kanthasamy AG. Impact of Environmental Risk Factors on Mitochondrial Dysfunction, Neuroinflammation, Protein Misfolding, and Oxidative Stress in the Etiopathogenesis of Parkinson’s Disease. Int J Mol Sci 2022, 23(18).

    Article  PubMed  PubMed Central  Google Scholar 

  • Slézia A, Hegedüs P, Rusina E, Lengyel K, Solari N, Kaszas A, Balázsfi D, Botzanowski B, Acerbo E, Missey F, et al. Behavioral, neural and ultrastructural alterations in a graded-dose 6-OHDA mouse model of early-stage Parkinson’s disease. Sci Rep. 2023;13(1):19478.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pyatha S, Kim H, Lee D, Kim K. Association between Heavy Metal Exposure and Parkinson’s Disease: A Review of the Mechanisms Related to Oxidative Stress. Antioxid (Basel) 2022, 11(12).

    Article  Google Scholar 

  • Reeve A, Simcox E, Turnbull D. Ageing and Parkinson’s disease: why is advancing age the biggest risk factor? Ageing Res Rev. 2014;14(100):19–30.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ludtmann MH, Angelova PR, Ninkina NN, Gandhi S, Buchman VL, Abramov AY. Monomeric Alpha-Synuclein exerts a physiological role on Brain ATP synthase. J Neurosci. 2016;36(41):10510–21.

    Article  PubMed  PubMed Central  Google Scholar 

  • Norris KL, Hao R, Chen LF, Lai CH, Kapur M, Shaughnessy PJ, Chou D, Yan J, Taylor JP, Engelender S, et al. Convergence of Parkin, PINK1, and α-Synuclein on stress-induced mitochondrial morphological remodeling. J Biol Chem. 2015;290(22):13862–74.

    Article  PubMed  PubMed Central  Google Scholar 

  • Devi L, Raghavendran V, Prabhu BM, Avadhani NG, Anandatheerthavarada HK. Mitochondrial Import and Accumulation of α-Synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson Disease Brain*. J Biol Chem. 2008;283(14):9089–100.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ludtmann MHR, Angelova PR, Horrocks MH, Choi ML, Rodrigues M, Baev AY, Berezhnov AV, Yao Z, Little D, Banushi B, et al. : α-synuclein oligomers interact with ATP synthase and open the permeability transition pore in Parkinson’s disease. Nat Commun. 2018;9(1):2293.

    Article  PubMed  PubMed Central  Google Scholar 

  • Esteves AR, Arduíno DM, Silva DF, Oliveira CR, Cardoso SM. Mitochondrial dysfunction: the Road to Alpha-Synuclein oligomerization in PD. Parkinsons Dis. 2011;2011:693761.

    PubMed  PubMed Central  Google Scholar 

  • Choi ML, Chappard A, Singh BP, Maclachlan C, Rodrigues M, Fedotova EI, Berezhnov AV, De S, Peddie CJ, Athauda D, et al. Pathological structural conversion of α-synuclein at the mitochondria induces neuronal toxicity. Nat Neurosci. 2022;25(9):1134–48.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lurette O, Martín-Jiménez R, Khan M, Sheta R, Jean S, Schofield M, Teixeira M, Rodriguez-Aller R, Perron I, Oueslati A, et al. Aggregation of alpha-synuclein disrupts mitochondrial metabolism and induce mitophagy via cardiolipin externalization. Cell Death Dis. 2023;14(11):729.

    Article  PubMed  PubMed Central  Google Scholar 

  • Schildknecht S, Gerding HR, Karreman C, Drescher M, Lashuel HA, Outeiro TF, Di Monte DA, Leist M. Oxidative and nitrative alpha-synuclein modifications and proteostatic stress: implications for disease mechanisms and interventions in synucleinopathies. J Neurochem. 2013;125(4):491–511.

    Article  PubMed  Google Scholar 

  • Li H-Y, Liu D-S, Zhang Y-B, Rong H, Zhang X-J. The interaction between alpha-synuclein and mitochondrial dysfunction in Parkinson’s disease. Biophys Chem. 2023;303:107122.

    Article  PubMed  Google Scholar 

  • Dias V, Junn E, Mouradian MM. The role of oxidative stress in Parkinson’s disease. J Parkinsons Dis. 2013;3(4):461–91.

    Article  PubMed  PubMed Central  Google Scholar 

  • Alam ZI, Jenner A, Daniel SE, Lees AJ, Cairns N, Marsden CD, Jenner P, Halliwell B. Oxidative DNA damage in the parkinsonian brain: an apparent selective increase in 8-hydroxyguanine levels in substantia nigra. J Neurochem. 1997;69(3):1196–203.

    Article  PubMed  Google Scholar 

  • Chalovich EM, Zhu J-h, Caltagarone J, Bowser R, Chu CT. Functional repression of cAMP response element in 6-Hydroxydopamine-treated neuronal cells. J Biol Chem. 2006;281(26):17870–81.

    Article  PubMed  Google Scholar 

  • Sakamoto K, Karelina K, Obrietan K. CREB: a multifaceted regulator of neuronal plasticity and protection. J Neurochem. 2011;116(1):1–9.

    Article  PubMed  Google Scholar 

  • Zhu JH, Kulich SM, Oury TD, Chu CT. Cytoplasmic aggregates of phosphorylated extracellular signal-regulated protein kinases in Lewy body diseases. Am J Pathol. 2002;161(6):2087–98.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ferrer I, Blanco R, Carmona M, Puig B, Barrachina M, Gómez C, Ambrosio S. Active, phosphorylation-dependent mitogen-activated protein kinase (MAPK/ERK), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and p38 kinase expression in Parkinson’s disease and dementia with Lewy bodies. J Neural Transm (Vienna). 2001;108(12):1383–96.

    Article  PubMed  Google Scholar 

  • Dagda RK, Zhu J, Kulich SM, Chu CT. Mitochondrially localized ERK2 regulates mitophagy and autophagic cell stress: implications for Parkinson’s disease. Autophagy. 2008;4(6):770–82.

    Article  PubMed  Google Scholar 

  • Maeder CI, Kim J-I, Liang X, Kaganovsky K, Shen A, Li Q, Li Z, Wang S, Xu XZS, Li JB, et al. The THO complex coordinates transcripts for Synapse Development and dopamine neuron survival. Cell. 2018;174(6):1436–e14491420.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bitetto G, Di Fonzo A. Nucleo–cytoplasmic transport defects and protein aggregates in neurodegeneration. Translational Neurodegeneration. 2020;9(1):1–16.

    Article  Google Scholar 

  • Goers J, Manning-Bog AB, McCormack AL, Millett IS, Doniach S, Di Monte DA, Uversky VN, Fink AL. Nuclear localization of alpha-synuclein and its interaction with histones. Biochemistry. 2003;42(28):8465–71.

    Article  PubMed  Google Scholar 

  • Zhou M, Xu S, Mi J, Uéda K, Chan P. Nuclear translocation of alpha-synuclein increases susceptibility of MES23.5 cells to oxidative stress. Brain Res. 2013;1500:19–27.

    Article  PubMed  Google Scholar 

  • Koss DJ, Erskine D, Porter A, Palmoski P, Menon H, Todd OGJ, Leite M, Attems J, Outeiro TF. Nuclear alpha-synuclein is present in the human brain and is modified in dementia with Lewy bodies. Acta Neuropathol Commun. 2022;10(1):98.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pinho R, Paiva I, Jercic KG, Fonseca-Ornelas L, Gerhardt E, Fahlbusch C, Garcia-Esparcia P, Kerimoglu C, Pavlou MAS, Villar-Piqué A, et al. Nuclear localization and phosphorylation modulate pathological effects of alpha-synuclein. Hum Mol Genet. 2019;28(1):31–50.

    Article  PubMed  Google Scholar 

  • Siddiqui A, Chinta SJ, Mallajosyula JK, Rajagopolan S, Hanson I, Rane A, Melov S, Andersen JK. Selective binding of nuclear alpha-synuclein to the PGC1alpha promoter under conditions of oxidative stress may contribute to losses in mitochondrial function: implications for Parkinson’s disease. Free Radic Biol Med. 2012;53(4):993–1003.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pasha T, Zatorska A, Sharipov D, Rogelj B, Hortobágyi T, Hirth F. Karyopherin abnormalities in neurodegenerative proteinopathies. Brain. 2021;144(10):2915–32.

    Article  PubMed  PubMed Central  Google Scholar 

  • Geertsma HM, Suk TR, Ricke KM, Horsthuis K, Parmasad J-LA, Fisk ZA, Callaghan SM, Rousseaux MWC. Constitutive nuclear accumulation of endogenous alpha-synuclein in mice causes motor impairment and cortical dysfunction, independent of protein aggregation. Hum Mol Genet. 2022;31(21):3613–28.

    Article  PubMed  PubMed Central  Google Scholar 

  • Schell H, Hasegawa T, Neumann M, Kahle PJ. Nuclear and neuritic distribution of serine-129 phosphorylated alpha-synuclein in transgenic mice. Neuroscience. 2009;160(4):796–804.

    Article  PubMed  Google Scholar 

  • Chen V, Moncalvo M, Tringali D, Tagliafierro L, Shriskanda A, Ilich E, Dong W, Kantor B, Chiba-Falek O. The mechanistic role of alpha-synuclein in the nucleus: impaired nuclear function caused by familial Parkinson’s disease SNCA mutations. Hum Mol Genet. 2020;29(18):3107–21.

    Article  PubMed  PubMed Central  Google Scholar 

  • Rousseaux MW, de Haro M, Lasagna-Reeves CA, De Maio A, Park J, Jafar-Nejad P, Al-Ramahi I, Sharma A, See L, Lu N et al. TRIM28 regulates the nuclear accumulation and toxicity of both alpha-synuclein and tau. Elife 2016, 5.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ma K-L, Song L-K, Yuan Y-H, Zhang Y, Han N, Gao K, Chen N-H. The nuclear accumulation of alpha-synuclein is mediated by importin alpha and promotes neurotoxicity by accelerating the cell cycle. Neuropharmacology. 2014;82:132–42.

    Article  PubMed  Google Scholar 

  • Tagliafierro L, Zamora ME, Chiba-Falek O. Multiplication of the SNCA locus exacerbates neuronal nuclear aging. Hum Mol Genet. 2019;28(3):407–21.

    Article  PubMed  Google Scholar 

  • Liu GH, Qu J, Suzuki K, Nivet E, Li M, Montserrat N, Yi F, Xu X, Ruiz S, Zhang W, et al. Progressive degeneration of human neural stem cells caused by pathogenic LRRK2. Nature. 2012;491(7425):603–7.

    Article  PubMed  PubMed Central  Google Scholar 

  • Shani V, Safory H, Szargel R, Wang N, Cohen T, Elghani FA, Hamza H, Savyon M, Radzishevsky I, Shaulov L, et al. Physiological and pathological roles of LRRK2 in the nuclear envelope integrity. Hum Mol Genet. 2019;28(23):3982–96.

    Article  PubMed  PubMed Central  Google Scholar 

  • Tsika E, Kannan M, Foo CS, Dikeman D, Glauser L, Gellhaar S, Galter D, Knott GW, Dawson TM, Dawson VL, et al. Conditional expression of Parkinson’s disease-related R1441C LRRK2 in midbrain dopaminergic neurons of mice causes nuclear abnormalities without neurodegeneration. Neurobiol Dis. 2014;71:345–58.

    Article  PubMed  PubMed Central  Google Scholar 

  • Um JW, Min DS, Rhim H, Kim J, Paik SR, Chung KC. Parkin Ubiquitinates and promotes the degradation of RanBP2*. J Biol Chem. 2006;281(6):3595–603.

    Article  PubMed  Google Scholar 

  • Cho K-i, Searle K, Webb M, Yi H, Ferreira PA. Ranbp2 haploinsufficiency mediates distinct cellular and biochemical phenotypes in brain and retinal dopaminergic and glia cells elicited by the parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Cell Mol Life Sci. 2012;69(20):3511–27.

    Article  PubMed  PubMed Central  Google Scholar 

  • Krisko A, Radman M. Protein damage, ageing and age-related diseases. Open Biol. 2019;9(3):180249.

    Article  PubMed  PubMed Central  Google Scholar 

  • Reeg S, Grune T. Protein oxidation in aging: does it play a role in aging progression? Antioxid Redox Signal. 2015;23(3):239–55.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kristiani L, Kim Y. The interplay between oxidative stress and the Nuclear Lamina contributes to Laminopathies and Age-Related diseases. In: Cells 12; 2023.

    Article  PubMed  PubMed Central  Google Scholar 

  • Heo J. Redox regulation of Ran GTPase. Biochem Biophys Res Commun. 2008;376(3):568–72.

    Article  PubMed  Google Scholar 

  • Chatterjee M, Paschal BM. Disruption of the ran system by Cysteine Oxidation of the Nucleotide Exchange factor RCC1. Mol Cell Biol. 2015;35(3):566–81.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kodiha M, Chu A, Matusiewicz N, Stochaj U. Multiple mechanisms promote the inhibition of classical nuclear import upon exposure to severe oxidative stress. Cell Death Differ. 2004;11(8):862–74.

    Article  PubMed  Google Scholar 

  • Datta S, Snow CJ, Paschal BM. A pathway linking oxidative stress and the ran GTPase system in progeria. Mol Biol Cell. 2014;25(8):1202–15.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kodiha M, Tran D, Qian C, Morogan A, Presley JF, Brown CM, Stochaj U. Oxidative stress mislocalizes and retains transport factor importin-α and nucleoporins Nup153 and Nup88 in nuclei where they generate high molecular mass complexes. Biochim et Biophys Acta (BBA) – Mol Cell Res. 2008;1783(3):405–18.

    Article  Google Scholar 

  • Crampton N, Kodiha M, Shrivastava S, Umar R, Stochaj U. Oxidative stress inhibits nuclear protein export by multiple mechanisms that target FG nucleoporins and Crm1. Mol Biol Cell. 2009;20(24):5106–16.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kodiha M, Stochaj U. Nuclear transport: a switch for the oxidative stress-signaling circuit? J Signal Transduct. 2012, 2012:208650.

  • Mahboubi H, Seganathy E, Kong D, Stochaj U. Identification of novel stress Granule Components that are involved in Nuclear Transport. PLoS ONE. 2013;8(6):e68356.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mizuguchi-Hata C, Ogawa Y, Oka M, Yoneda Y. Quantitative regulation of nuclear pore complex proteins by O-GlcNAcylation. Biochim Biophys Acta. 2013;1833(12):2682–9.

    Article  PubMed  Google Scholar 

  • Kosako H, Imamoto N. Phosphorylation of nucleoporins: signal transduction-mediated regulation of their interaction with nuclear transport receptors. Nucleus (Austin Tex). 2010;1(4):309–13.

    PubMed  Google Scholar 

  • Faustino RS, Maddaford TG, Pierce GN. Mitogen activated protein kinase at the nuclear pore complex. J Cell Mol Med. 2011;15(4):928–37.

    Article  PubMed  Google Scholar 

  • Kodiha M, Bański P, Stochaj U. Interplay between MEK and PI3 kinase signaling regulates the subcellular localization of protein kinases ERK1/2 and akt upon oxidative stress. FEBS Lett. 2009;583(12):1987–93.

    Article  PubMed  Google Scholar 

  • Zachara NE, O’Donnell N, Cheung WD, Mercer JJ, Marth JD, Hart GW. Dynamic O-GlcNAc modification of Nucleocytoplasmic Proteins in response to stress: a SURVIVAL RESPONSE OF MAMMALIAN CELLS*. J Biol Chem. 2004;279(29):30133–42.

    Article  PubMed  Google Scholar 

  • Kátai E, Pál J, Poór VS, Purewal R, Miseta A, Nagy T. Oxidative stress induces transient O-GlcNAc elevation and tau dephosphorylation in SH-SY5Y cells. J Cell Mol Med. 2016;20(12):2269–77.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kodiha M, Tran D, Morogan A, Qian C, Stochaj U. Dissecting the signaling events that impact classical nuclear import and target nuclear transport factors. PLoS ONE. 2009;4(12):e8420.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee BE, Kim HY, Kim HJ, Jeong H, Kim BG, Lee HE, Lee J, Kim HB, Lee SE, Yang YR, et al. O-GlcNAcylation regulates dopamine neuron function, survival and degeneration in Parkinson disease. Brain. 2020;143(12):3699–716.

    Article  PubMed  PubMed Central  Google Scholar 

  • Tavassoly O, Yue J, Vocadlo DJ. Pharmacological inhibition and knockdown of O-GlcNAcase reduces cellular internalization of α-synuclein preformed fibrils. Febs j. 2021;288(2):452–70.

    Article  PubMed  Google Scholar 

  • Levine PM, Galesic A, Balana AT, Mahul-Mellier AL, Navarro MX, De Leon CA, Lashuel HA, Pratt MR. α-Synuclein O-GlcNAcylation alters aggregation and toxicity, revealing certain residues as potential inhibitors of Parkinson’s disease. Proc Natl Acad Sci U S A. 2019;116(5):1511–9.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hart GW, Housley MP, Slawson C. Cycling of O-linked β-N-acetylglucosamine on nucleocytoplasmic proteins. Nature. 2007;446(7139):1017–22.

    Article  PubMed  Google Scholar 

  • Coyne AN, Rothstein JD. Nuclear pore complexes — a doorway to neural injury in neurodegeneration. Nat Reviews Neurol. 2022;18(6):348–62.

    Article  Google Scholar 

  • Masrori P, Van Damme P. Amyotrophic lateral sclerosis: a clinical review. Eur J Neurol. 2020;27(10):1918–29.

    Article  PubMed  Google Scholar 

  • Zhang J, Ito H, Wate R, Ohnishi S, Nakano S, Kusaka H. Altered distributions of nucleocytoplasmic transport-related proteins in the spinal cord of a mouse model of amyotrophic lateral sclerosis. Acta Neuropathol. 2006;112(6):673–80.

    Article  PubMed  Google Scholar 

  • Jovičić A, Mertens J, Boeynaems S, Bogaert E, Chai N, Yamada SB, Paul JW, Sun S, Herdy JR, Bieri G, et al. Modifiers of C9orf72 dipeptide repeat toxicity connect nucleocytoplasmic transport defects to FTD/ALS. Nat Neurosci. 2015;18(9):1226–9.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang K, Donnelly CJ, Haeusler AR, Grima JC, Machamer JB, Steinwald P, Daley EL, Miller SJ, Cunningham KM, Vidensky S, et al. The C9orf72 repeat expansion disrupts nucleocytoplasmic transport. Nature. 2015;525(7567):56–61.

    Article  PubMed  PubMed Central  Google Scholar 

  • Freibaum BD, Lu Y, Lopez-Gonzalez R, Kim NC, Almeida S, Lee K-H, Badders N, Valentine M, Miller BL, Wong PC, et al. GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport. Nature. 2015;525(7567):129–33.

    Article  PubMed  PubMed Central  Google Scholar 

  • Coyne AN, Baskerville V, Zaepfel BL, Dickson DW, Rigo F, Bennett F, Lusk CP, Rothstein JD. Nuclear accumulation of CHMP7 initiates nuclear pore complex injury and subsequent TDP-43 dysfunction in sporadic and familial ALS. Sci Transl Med. 2021, 13(604).

  • Chou C-C, Zhang Y, Umoh ME, Vaughan SW, Lorenzini I, Liu F, Sayegh M, Donlin-Asp PG, Chen YH, Duong DM, et al. TDP-43 pathology disrupts nuclear pore complexes and nucleocytoplasmic transport in ALS/FTD. Nat Neurosci. 2018;21(2):228–39.

    Article  PubMed  PubMed Central  Google Scholar 

  • Giampetruzzi A, Danielson EW, Gumina V, Jeon M, Boopathy S, Brown RH, Ratti A, Landers JE, Fallini C. Modulation of actin polymerization affects nucleocytoplasmic transport in multiple forms of amyotrophic lateral sclerosis. Nat Commun. 2019;10(1):3827.

    Article  PubMed  PubMed Central  Google Scholar 

  • Shang J, Yamashita T, Nakano Y, Morihara R, Li X, Feng T, Liu X, Huang Y, Fukui Y, Hishikawa N, et al. Aberrant distributions of nuclear pore complex proteins in ALS mice and ALS patients. Neuroscience. 2017;350:158–68.

    Article  PubMed  Google Scholar 

  • Trist BG, Hilton JB, Hare DJ, Crouch PJ, Double KL. Superoxide dismutase 1 in Health and Disease: how a Frontline antioxidant becomes neurotoxic. Angew Chem Int Ed Engl. 2021;60(17):9215–46.

    Article  PubMed  Google Scholar 

  • Erkkinen MG, Kim MO, Geschwind MD. Clinical neurology and epidemiology of the Major Neurodegenerative diseases. Cold Spring Harb Perspect Biol 2018, 10(4).

    Article  PubMed  PubMed Central  Google Scholar 

  • Twohig D, Nielsen HM. α-synuclein in the pathophysiology of Alzheimer’s disease. Mol Neurodegener. 2019;14(1):23.

    Article  PubMed  PubMed Central  Google Scholar 

  • Eftekharzadeh B, Daigle JG, Kapinos LE, Coyne A, Schiantarelli J, Carlomagno Y, Cook C, Miller SJ, Dujardin S, Amaral AS, et al. Tau protein disrupts nucleocytoplasmic transport in Alzheimer’s Disease. Neuron. 2018;99(5):925–e940927.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang X, Gao F, Wang D, Li C, Fu Y, He W, Zhang J. Tau Pathology in Parkinson’s Disease. Front Neurol. 2018;9:809.

    Article  PubMed  PubMed Central  Google Scholar 

  • Leone L, Colussi C, Gironi K, Longo V, Fusco S, Li Puma DD, D’Ascenzo M, Grassi C. Altered Nup153 expression impairs the function of cultured hippocampal neural stem cells isolated from a mouse model of Alzheimer’s Disease. Mol Neurobiol. 2019;56(8):5934–49.

    Article  PubMed  Google Scholar 

  • Malik SC, Lin JD, Ziegler-Waldkirch S, Tholen S, Deshpande SS, Schwabenland M, Schilling O, Vlachos A, Meyer-Luehmann M, Schachtrup C. Tpr Misregulation in Hippocampal Neural Stem Cells in Mouse Models of Alzheimer’s Disease. Cells 2023, 12(23).

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee BE, Suh P-G, Kim J-I. O-GlcNAcylation in health and neurodegenerative diseases. Exp Mol Med. 2021;53(11):1674–82.

    Article  PubMed  PubMed Central  Google Scholar 

  • Grima JC, Daigle JG, Arbez N, Cunningham KC, Zhang K, Ochaba J, Geater C, Morozko E, Stocksdale J, Glatzer JC, et al. Mutant huntingtin disrupts the Nuclear Pore Complex. Neuron. 2017;94(1):93–e107106.

    Article  PubMed  PubMed Central  Google Scholar 

  • Flokas ME, Tomani M, Agdere L, Brown B. Triple A syndrome (Allgrove syndrome): improving outcomes with a multidisciplinary approach. Pediatr Health Med Ther. 2019;10:99–106.

    Article  Google Scholar 

  • Cronshaw JM, Matunis MJ. The nuclear pore complex protein ALADIN is mislocalized in triple A syndrome. Proc Natl Acad Sci U S A. 2003;100(10):5823–7.

    Article  PubMed  PubMed Central  Google Scholar 

  • Storr HL, Kind B, Parfitt DA, Chapple JP, Lorenz M, Koehler K, Huebner A, Clark AJ. Deficiency of ferritin heavy-chain nuclear import in triple a syndrome implies nuclear oxidative damage as the primary disease mechanism. Mol Endocrinol. 2009;23(12):2086–94.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hirano M, Furiya Y, Asai H, Yasui A, Ueno S. ALADIN I482S causes selective failure of nuclear protein import and hypersensitivity to oxidative stress in triple A syndrome. Proc Natl Acad Sci. 2006;103(7):2298–303.

    Article  PubMed  PubMed Central  Google Scholar 

  • Tsai YL, Coady TH, Lu L, Zheng D, Alland I, Tian B, Shneider NA, Manley JL. ALS/FTD-associated protein FUS induces mitochondrial dysfunction by preferentially sequestering respiratory chain complex mRNAs. Genes Dev. 2020;34(11–12):785–805.

    Article  PubMed  PubMed Central  Google Scholar 

  • Teyssou E, Chartier L, Roussel D, Perera ND, Nemazanyy I, Langui D, Albert M, Larmonier T, Saker S, Salachas F et al. The amyotrophic lateral sclerosis M114T PFN1 mutation deregulates alternative Autophagy pathways and mitochondrial homeostasis. Int J Mol Sci 2022, 23(10).

    Article  PubMed  PubMed Central  Google Scholar 

  • Ganjam GK, Bolte K, Matschke LA, Neitemeier S, Dolga AM, Höllerhage M, Höglinger GU, Adamczyk A, Decher N, Oertel WH, et al. Mitochondrial damage by α-synuclein causes cell death in human dopaminergic neurons. Cell Death Dis. 2019;10(11):865.

    Article  PubMed  PubMed Central  Google Scholar 

  • Delcambre S, Ghelfi J, Ouzren N, Grandmougin L, Delbrouck C, Seibler P, Wasner K, Aasly JO, Klein C, Trinh J et al. Mitochondrial mechanisms of LRRK2 G2019S Penetrance. Front Neurol 2020, 11.

    Article  PubMed  PubMed Central  Google Scholar 

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