TY - JOUR
T1 - Does Developmental Variability in the Number of Midbrain Dopamine Neurons Affect Individual Risk for Sporadic Parkinson's Disease?
AU - Von Linstow, Christian U.
AU - Delano-Taylor, Merritt
AU - Kordower, Jeffrey H.
AU - Brundin, Patrik
N1 - Publisher Copyright:
© 2020-IOS Press and the authors. All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Parkinson's disease risk
KW - cis-regulation
KW - dopamine neuron number
KW - motor dysfunction
KW - neural development
KW - substantia nigra
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U2 - 10.3233/JPD-191877
DO - 10.3233/JPD-191877
M3 - Review article
C2 - 31958098
AN - SCOPUS:85083041734
SN - 1877-7171
VL - 10
SP - 405
EP - 411
JO - Journal of Parkinson's Disease
JF - Journal of Parkinson's Disease
IS - 2
ER -