Is Alpha-Synuclein Loss-of-Function a Contributor to Parkinsonian Pathology? Evidence from Non-human Primates
Accumulation of alpha-synuclein (α-syn) in Lewy bodies and neurites of midbrain dopamine neurons is diagnostic for Parkinson's disease (PD), leading to the proposal that PD is a toxic gain-of-function synucleinopathy. Here we discuss the alternative viewpoint that α-syn displacement from synapses by misfolding and aggregation results in a toxic loss-of-function. In support of this hypothesis we provide evidence from our pilot study demonstrating that knockdown of endogenous α-syn in dopamine neurons of non-human primates reproduces the pattern of nigrostriatal degeneration characteristic of PD.
Parkinson's disease, alpha-synuclein, dopamine, non-human primates, substantia nigra
Frontiers in neuroscience
Digital Object Identifier (DOI)
Collier, Timothy J.; Redmond, D Eugene; Steece-Collier, Kathy; Lipton, Jack W.; and Manfredsson, Fredric P., "Is Alpha-Synuclein Loss-of-Function a Contributor to Parkinsonian Pathology? Evidence from Non-human Primates" (2016). Translational Neuroscience. 1431.