AUTHOR=Collier Timothy J. , Redmond D. Eugene , Steece-Collier Kathy , Lipton Jack W. , Manfredsson Fredric P. 

TITLE=Is Alpha-Synuclein Loss-of-Function a Contributor to Parkinsonian Pathology? Evidence from Non-human Primates

JOURNAL=Frontiers in Neuroscience

VOLUME=10

YEAR=2016

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2016.00012

DOI=10.3389/fnins.2016.00012

ISSN=1662-453X

ABSTRACT=<p>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.</p>