PGC-1α at the intersection of bioenergetics regulation and neuron function: From Huntington's disease to Parkinson's disease and beyond

Taiji Tsunemi, Albert R. La Spada*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

81 Scopus citations

Abstract

Neurons are specialized cells with unique features, including a constant high demand for energy. Mitochondria satisfy this constant demand, and are emerging as a central target for dysfunction in neurodegenerative disorders, such as Huntington's disease (HD) and Parkinson's disease. PPARγ co-activator-1α (PGC-1α) is a transcription co-activator for nuclear receptors such as the PPARs, and thereby coordinates a number of gene expression programs to promote mitochondrial biogenesis and oxidative phosphorylation. Studies of PGC-1α knock-out mice have yielded important insights into the role of PGC-1α in normal nervous system function and potentially neurological disease. HD is caused by a polyglutamine repeat expansion in the huntingtin protein, and decades of work have established mitochondrial dysfunction as a key feature of HD pathogenesis. However, after the discovery of the HD gene, numerous reports produced strong evidence for altered transcription in HD. In 2006, a series of studies revealed that PGC-1α transcription interference contributes to HD neurodegeneration, linking the nuclear transcriptionopathy with the mitochondrial dysfunction. Subsequent work has strengthened this view, and further extended the role of PGC-1α within the CNS. Within the last year, studies of Parkinson's disease, another involuntary movement disorder long associated with mitochondrial dysfunction, have shown that PGC-1α dysregulation is contributing to its pathogenesis. As PGC-1α is likely also important for aging, a process with considerable relevance to neuron function, translational studies aimed at developing therapies based upon the PGC-1α pathway as a high priority target are underway.

Original languageEnglish (US)
Pages (from-to)142-151
Number of pages10
JournalProgress in Neurobiology
Volume97
Issue number2
DOIs
StatePublished - May 2012

Keywords

  • Huntington's disease
  • Mitochondria
  • Neurodegeneration
  • PGC-1α
  • Parkinson's disease
  • Transcription

ASJC Scopus subject areas

  • Neuroscience(all)

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