α-synuclein aggregation reduces nigral myocyte enhancer Factor-2D in idiopathic and experimental Parkinson's disease

Yaping Chu, Amanda L. Mickiewicz, Jeffrey H. Kordower

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

α-synuclein is an abundant neuronal protein that has been linked to both normal synaptic function and neurodegenerative disease, in particular, Parkinson's disease (PD). Evidence from both in vitro and in vivo studies indicate that increased wild type or mutant α-synuclein can cause PD, but the molecular mechanisms that underlie α-synuclein-mediated neurotoxicity remain poorly understood. We reported here that myocyte enhancer factor 2D (MEF2D), a nuclear transcription factor known to promote neuronal survival, is down regulated in response α-synuclein accumulation and aggregation. Our data demonstrated that levels of cytoplasmic and nuclear MEF2D were significantly decreased in PD nigral neurons when compared to the nigra of age-matched controls and Alzheimer's disease (AD) cases. This decrease was significantly greater in the nigral neurons with α-synuclein inclusions. Viral vector-mediated overexpression of human α-synuclein in rats resulted in significantly decreased MEF2D in nigral neurons similar to what was seen in PD. The decline of MEF2D-immunoreactivity was associated with a reduction in TH-immunoreactivity. These results indicate that the neuronal survival factor MEF2D is decreased in human and experimental PD, and this decrease is specifically associated with α-synuclein accumulation and aggregation.

Original languageEnglish (US)
Pages (from-to)71-82
Number of pages12
JournalNeurobiology of Disease
Volume41
Issue number1
DOIs
StatePublished - Jan 2011
Externally publishedYes

Keywords

  • Alpha-synuclein
  • Dopaminergic neuron
  • Myocyte enhancer factor 2D
  • Parkinson's disease
  • Substantia nigra

ASJC Scopus subject areas

  • Neurology

Fingerprint

Dive into the research topics of 'α-synuclein aggregation reduces nigral myocyte enhancer Factor-2D in idiopathic and experimental Parkinson's disease'. Together they form a unique fingerprint.

Cite this