Parkinson's Blog

Background Variants in the CTSB gene encoding the lysosomal hydrolase cathepsin B (catB) are associated with increased risk of Parkinson’s disease (PD). However, neither the specific CTSB variants driving these associations nor the functional pathways that link catB to PD pathogenesis have been characterized. CatB activity contributes to lysosomal protein degradation and regulates signaling processes involved in autophagy and lysosome biogenesis. Previous in vitro studies have found that catB can cleave monomeric and fibrillar alpha-synuclein, a key protein involved in the pathogenesis of PD that accumulates in the brains of PD patients. However, truncated synuclein isoforms generated by catB cleavage have an increased propensity to aggregate. Thus, catB activity could potentially contribute to lysosomal degradation and clearance of pathogenic alpha synuclein from the cell, but also has the potential of enhancing synuclein pathology by generating aggregation-prone truncations. Therefore, the mechanisms linking catB to PD pathophysiology remain to be clarified. Methods Here, we conducted genetic analyses of the association between common and rare CTSB variants and risk of PD. We then used genetic and pharmacological approaches to manipulate catB expression and function in cell lines, induced pluripotent stem cell-derived dopaminergic neurons and midbrain organoids and assessed lysosomal activity and the handling of aggregated synuclein fibrils. Results We find that catB inhibition impairs autophagy, reduces glucocerebrosidase (encoded by GBA1) activity, and leads to an accumulation of lysosomal content. In cell lines, reduction of CTSB gene expression impairs the degradation of pre-formed alpha-synuclein fibrils, whereas CTSB gene activation enhances fibril clearance. In midbrain organoids and dopaminergic neurons treated with alpha-synuclein fibrils, catB inhibition potentiates the formation of inclusions which stain positively for phosphorylated alpha-synuclein. Conclusions These results indicate that the reduction of catB function negatively impacts lysosomal pathways associated with PD pathogenesis, while conversely catB activation could promote the clearance of pathogenic alpha-synuclein.

NFL News: NFL legend Brett Favre has revealed his battle with Parkinson’s disease. Diagnosed after experiencing arm issues, Favre experiences stiffness and diff

Former NFL quarterback Brett Favre opened in a recent interview about about living with Parkinson’s disease and his hope for the future.

Wrexham ran out 3-0 winners over Exeter City in League One on Saturday, thanks to goals from Max Cleworth, Ollie Palmer and Oliver Rathbone.

Two Kolkata men in their 60s, one battling Parkinson’s disease and the other cervical dystonia, have found relief from debilitating symptoms thanks to

Nuclear pore complexes (NPCs) are embedded in the nuclear envelope and facilitate the exchange of macromolecules between the nucleus and cytoplasm in eukaryotic cells. The dysfunction of the NPC and nuclear transport plays a significant role in aging and the pathogenesis of various neurodegenerative diseases. Common features among these neurodegenerative diseases, including Parkinson’s disease (PD), encompass mitochondrial dysfunction, oxidative stress and the accumulation of insoluble protein aggregates in specific brain regions. The susceptibility of dopaminergic neurons to mitochondrial stress underscores the pivotal role of mitochondria in PD progression. Disruptions in mitochondrial-nuclear communication are exacerbated by aging and α-synuclein-induced oxidative stress in PD. The precise mechanisms underlying mitochondrial impairment-induced neurodegeneration in PD are still unclear. Evidence suggests that perturbations in dopaminergic neuronal nuclei are linked to PD-related neurodegeneration. These perturbations involve structural damage to the nuclear envelope and mislocalization of pivotal transcription factors, potentially driven by oxidative stress or α-synuclein pathology. The presence of protein aggregates, pathogenic mutations, and ongoing oxidative stress can exacerbate the dysfunction of NPCs, yet this mechanism remains understudied in the context of oxidative stress-induced PD. This review summarizes the link between mitochondrial dysfunction and dopaminergic neurodegeneration and outlines the current evidence for nuclear envelope and nuclear transport abnormalities in PD, particularly in oxidative stress. We highlight the potential role of nuclear pore and nucleocytoplasmic transport dysfunction in PD and stress the importance of systematically investigating NPC components in PD.

Background Over the past few years, the development of telerehabilitation has advanced rapidly. Patients with Parkinson’s disease (PwPD) often have difficulty with mobility, making it challenging for them to perform centre-based exercise.This study aims to compare the effectiveness and adherence of home physical therapy (HPT) and telerehabilitation (TR) in mitigating motor symptoms and improving the quality of life in patients with mild to moderate Parkinson’s disease. Methods This randomized controlled trial included a total of 190 patients who underwent in-person eligibility assessment, with 100 allocated to the HPT group and 90 to the TR group. Both interventions consisted of home-based training sessions lasting 40–60 min and were conducted five times a week for 4 weeks. The primary outcome was the Unified Parkinson’s Disease Rating Scale motor section (UPDRS3) score. Secondary outcomes included balance function, assessed using the Berg Balance Scale (BBS); risk of fall, evaluated through the Timed Up-and-Go test (TUG) and the Five Times Sit-to-Stand test (FTSST); gait, measured using the Freezing of Gait Questionnaire (FOGQ) and IDEEA activity monitor; muscle strength, evaluated using the isokinetic dynamometry; motor aspects of experiences of daily living (UPDRS2); and quality of life, assessed by Parkinson’s Disease Questionnaire-39 (PDQ-39). Results There was a significant difference in the UPDRS3, BBS, TUG, FTSST, FOGQ,step length, step velocity,preswing angle, UPDRS2 and PDQ-39 between baseline and 4 weeks in both groups. The decrease in the UPDRS3 score was significantly greater in the HPT group (-3.38 points) than in the RE group (-1.45 points) in the older age group (P = 0.021), but there was no significant between-group difference in the younger age group (P = 0.416). Similar changes favouring the HPT group were observed in the BBS, TUG, step velocity, and extension average torque. 7 (7%) patients in the HPT group and 12 (13%) patients in the TR group did not complete their daily exercise plan. Conclusions Both HPT and TR have demonstrated effectiveness, safety, and feasibility in PwPD. However, the HPT program exhibited greater effectiveness among older patients and higher patient compliance compared to TR. Trial registration Chictr.org.cn, ChiCTR2300071648. Registered on 22 May 2023—retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=196313 .

The Parkinson’s drug entacapone disrupts the gut microbiome by inducing iron deficiency, favoring the growth of potentially harmful bacteria like E. coli.

Upper Limits Rock Gym and Pro Shop in Bloomington host monthly classes for people living with Parkinson’s Disease, proving climbing is for everyone.

Scientific Reports – A qualitative study exploring the clinical phenomenology and impact of hypersexuality in patients with Parkinson’s Disease