Journal
JOURNAL OF PARKINSONS DISEASE
Volume 10, Issue 2, Pages 405-411Publisher
IOS PRESS
DOI: 10.3233/JPD-191877
Keywords
Parkinson's disease risk; dopamine neuron number; substantia nigra; neural development; motor dysfunction; cis-regulation
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Funding
- National Institutes of Health [1R01DC016519-01, 5R21NS 093993-02, 1R21NS106078-01A1]
- Office of the Assistant Secretary of Defense for Health Affairs (Parkinson's Research Program) [W81XWH-17-10534]
- Peter C. and Emajean Cook Foundation
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Parkinson's disease (PD) is a slowly progressing neurodegenerative disorder that is coupled to both widespread protein aggregation and to loss of substantia nigra dopamine (DA) neurons, resulting in a wide variety of motor and non-motor signs and symptoms. Recent findings suggest that the PD process is triggered several years before there is sufficient degeneration of DA neurons to cause onset of overt motor symptoms. According to this concept, the number of DA neurons present in the substantia nigra at birth could influence the time from the molecular triggering event until the clinical diagnosis with lower number of neurons at birth increasing the risk to develop the disease. Conversely, the risk for diagnosis would be reduced if the number of DA neurons is high at birth. In this commentary, we discuss the genetic and epigenetic factors that might influence the number of nigral DA neurons that each individual is born with and how these may be linked to PD risk.
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