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 synaps...

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Veröffentlicht in:Frontiers in neuroscience 2016-01, Vol.10, p.12-12
Hauptverfasser: Collier, Timothy J, Redmond, Jr, D Eugene, Steece-Collier, Kathy, Lipton, Jack W, Manfredsson, Fredric P
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Sprache:eng
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Zusammenfassung: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.
ISSN:1662-4548
1662-453X
1662-453X
DOI:10.3389/fnins.2016.00012