A5088732447- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Nuclear Receptors and Signaling
- Neurological diseases and metabolism
- Autism Spectrum Disorder Research
- Neuroscience and Neuropharmacology Research
- Nerve injury and regeneration
- Lysosomal Storage Disorders Research
- Alzheimer's disease research and treatments
- Biochemical and biochemical processes
- Biomedical Ethics and Regulation
- Health Systems, Economic Evaluations, Quality of Life
- Pharmaceutical Economics and Policy
- Aldose Reductase and Taurine
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Ethics in Clinical Research
- Health and Medical Research Impacts
- Biotechnology and Related Fields
- Biotin and Related Studies
- Neuropeptides and Animal Physiology
- Plant Gene Expression Analysis
- Scientific Computing and Data Management
- Dementia and Cognitive Impairment Research
- Ginkgo biloba and Cashew Applications
Michael J. Fox Foundation
2016-2025
Center for Open Science
2021
University of California, San Francisco
2021
Krembil Research Institute
2019-2020
Toronto Western Hospital
2019-2020
McGill University
2020
University of Toronto
2019
Emory University
2000-2014
Innsbruck Medical University
2013
National and Kapodistrian University of Athens
2009
Exposure of rats to the pesticide and complex I inhibitor rotenone reproduces features Parkinson's disease, including selective nigrostriatal dopaminergic degeneration alpha-synuclein-positive cytoplasmic inclusions (Betarbet et al., 2000; Sherer 2003). Here, we examined mechanisms toxicity using three model systems. In SK-N-MC human neuroblastoma cells, (10 nm 1 microm) caused dose-dependent ATP depletion, oxidative damage, death. To determine molecular site action rotenone, cells were...
Chronic systemic complex I inhibition caused by rotenone exposure induces features of Parkinson's disease (PD) in rats, including selective nigrostriatal dopaminergic degeneration and formation ubiquitin- alpha-synuclein-positive inclusions (Betarbet et al., 2000). To determine underlying mechanisms rotenone-induced cell death, we developed a chronic vitro model based on treating human neuroblastoma cells with 5 nm for 1-4 weeks. For up to 4 weeks, grown the presence had normal morphology...
Abstract Objective The Parkinson's Progression Markers Initiative ( PPMI ) is an observational, international study designed to establish biomarker‐defined cohorts and identify clinical, imaging, genetic, biospecimen disease PD progression markers accelerate disease‐modifying therapeutic trials. Methods A total of 423 untreated , 196 Healthy Control HC 64 SWEDD (scans without evidence dopaminergic deficit) subjects were enrolled at 24 sites. To enroll as early possible following diagnosis,...
<h3>Importance</h3> We observed a significant correlation between cerebrospinal fluid (CSF) levels of tau proteins and α-synuclein, but not β-amyloid 1-42 (Aβ1-42), lower concentration CSF biomarkers, as compared with healthy controls, in cohort entirely untreated patients Parkinson disease (PD) at the earliest stage studied so far. <h3>Objective</h3> To evaluate baseline characteristics relationship to clinical features biomarkers (Aβ1-42, total [T-tau], phosphorylated threonine 181...
LRRK2 kinase inhibitors, under development for Parkinson’s disease, have an effect on type II pneumocytes in nonhuman primate lung, suggesting that pulmonary toxicity may be a critical safety liability.
Abstract Parkinson’s disease (PD) has been linked to mitochondrial dysfunction and pesticide exposure. The rotenone (ROT) inhibits complex I reproduces features of PD in animal models, suggesting that environmental agents inhibit may contribute PD. We have previously demonstrated ROT toxicity is dependent upon inhibition oxidative stress the primary mechanism toxicity. In this study, we examined vitro action several putative inhibitors are commonly used as pesticides. rank order pesticides...
Recessively inherited loss-of-function mutations in the PTEN-induced putative kinase 1(Pink1), DJ-1 (Park7) and Parkin (Park2) genes are linked to familial cases of early-onset Parkinson's disease (PD). As part its strategy provide more tools for research community, The Michael J. Fox Foundation Research (MJFF) funded generation novel rat models with targeted disruption ofPink1, or determined if loss these proteins would result a progressive PD-like phenotype. Pathological, neurochemical...
ABSTRACT Objective: The objective of this study was to assess longitudinal change in clinical and dopamine transporter imaging outcomes early, untreated PD. Methods: We describe 5‐year the MDS‐UPDRS other measures using results from Parkinson's Progression Markers Initiative, a cohort early disease (PD) participants at baseline. also provide data on 123‐I Ioflupane striatal binding correlation between 2 measures. Results: A total 423 PD were recruited, 358 remain year 5. Baseline score 32.4...
Most approaches to machine learning from electronic health data can only predict a single endpoint. The ability simultaneously simulate dozens of patient characteristics is crucial step towards personalized medicine for Alzheimer's Disease. Here, we use an unsupervised model called Conditional Restricted Boltzmann Machine (CRBM) detailed trajectories. We comprising 18-month trajectories 44 clinical variables 1909 patients with Mild Cognitive Impairment or Disease train forecasting disease...
The Global Burden of Disease study conducted between 1990 and 2016, based on a global 195 countries territories, identified Parkinson disease (PD) as the fastest growing neurological disorder when measured using death disability. Most people affected by PD live in low- middle-income (LMICs) experience large inequalities access to care essential medicines. This Special Communication describes 6 actions steps that are urgently needed address disparities PD. adoption 73rd World Health Assembly...
Chronic infusion of rotenone (Rot) to Lewis rats reproduces many features Parkinson disease. Rot (3 mg/kg/day) was infused subcutaneously male for 6 days using Alzet minipumps. Control received the vehicle only. Presence 0.1% bovine serum albumin during isolation procedure completely removed bound mitochondria. Therefore all functional changes observed were aftereffects toxicity in vivo. In rat brain mitochondria (Rot-RBM) there a 30-40% inhibition respiration State 3 and 3U with Complex I...
Paraquat, MPTP, and rotenone reproduce features of Parkinson's disease (PD) in experimental animals. The exact mechanisms by which these compounds damage the dopamine system are not firmly established, but selective to neurons inhibition complex I thought be involved. We others have previously documented that toxic metabolite MPP+, is transported into through transporter (DAT), while DAT. also demonstrated requirement for oxidative dopaminergic neurodegeneration produced rotenone. Based on...