scholarly journals Cell metabolism affects selective vulnerability in PINK1-associated Parkinson's disease

2011 ◽  
Vol 124 (24) ◽  
pp. 4194-4202 ◽  
Author(s):  
Zhi Yao ◽  
Sonia Gandhi ◽  
Victoria S. Burchell ◽  
Helene Plun-Favreau ◽  
Nicholas W. Wood ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Metabolism ◽  
Selective Vulnerability

scholarly journals COVID-19 and selective vulnerability to Parkinson's disease

2020 ◽  
Vol 19 (9) ◽  
pp. 719 ◽  
Author(s):  
Alexandra Pavel ◽  
Danielle K Murray ◽  
A Jon Stoessl
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Selective Vulnerability

Calcium Channels as a Potential Target for Neuroprotection in Parkinson’s Disease

US Neurology ◽  
2011 ◽  
Vol 07 (02) ◽  
pp. 109 ◽  
Author(s):  
Tanya Simuni ◽  
D James Surmeier ◽  
◽  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuroprotective Effect ◽  
Selective Vulnerability ◽  
Phase Iii ◽  
Substantia Nigra Pars Compacta ◽  
Double Blind ◽  
Finding Study

Parkinson's disease (PD) is the second most common neurodegenerative disease affecting 1 % of the population above the age 65. The principal motor symptoms of PD are attributable to the preferential loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Recent studies demonstrate that dopaminergic (DA) neurons in the SNc, as well as many neurons in other regions affected by PD, have a distinctive physiologic phenotype. They are autonomous L-type Cav1.3 Ca2+channels pacemakers. Continuous Ca2+influx results in increased oxidative stress that may explain the selective vulnerability of these neurons. More importantly for PD, blocking these channels with isradipine, the most potent of the dihydropyridine (DHP) channel antagonists at L-type Ca2+channels with the Cav1.3 subunit, protects these neurons inin vitroandin vivomodels of parkinsonism. Neuroprotective effect is achieved at the serum concentrations that can be achieved with the doses approved for human use. Recent epidemiologic data also points to a reduced risk of PD with chronic use of specifically centrally acting DHP Ca2+channel antagonists. Isradipine is an approved agent for the treatment of hypertension. Our pilot data demonstrate acceptable dose-dependent tolerability of isradipine in early PD. A pilot Phase II multicenter, double-blind, placebo-controlled, safety, tolerability, and dosage finding study of isradipine in early PD has completed recruitment, with the results of the study to be available in the near future. Results of that study will inform the design of the planned Phase III pivotal efficacy trial of isradipine, as a disease modifying agent in early PD.

scholarly journals Calcium homeostasis, selective vulnerability and Parkinson's disease

2009 ◽  
Vol 32 (5) ◽  
pp. 249-256 ◽  
Author(s):  
C. Savio Chan ◽  
Tracy S. Gertler ◽  
D. James Surmeier
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Calcium Homeostasis ◽  
Selective Vulnerability

scholarly journals Parkin promotes proteasomal degradation of p62: implication of selective vulnerability of neuronal cells in the pathogenesis of Parkinson’s disease

2016 ◽  
Vol 7 (2) ◽  
pp. 114-129 ◽  
Author(s):  
Pingping Song ◽  
Shanshan Li ◽  
Hao Wu ◽  
Ruize Gao ◽  
Guanhua Rao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuronal Cells ◽  
Proteasomal Degradation ◽  
Selective Vulnerability
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