The PPARGC1A locus and CNS-specific PGC-1α isoforms are associated with Parkinson's Disease

Neurobiology of Disease
Selma M SoyalWolfgang Patsch

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. PGC-1α, encoded by PPARGC1A, is a transcriptional co-activator that has been implicated in the pathogenesis of neurodegenerative disorders. We recently discovered multiple new PPARGC1A transcripts that initiate from a novel promoter located far upstream of the reference gene promoter, are CNS-specific and are more abundant than reference gene transcripts in whole brain. These CNS-specific transcripts encode two main full-length and several truncated isoforms via alternative splicing. Truncated CNS-isoforms include 17 kDa proteins that lack the second LXXLL motif serving as an interaction site for several nuclear receptors. We now determined expression levels of CNS- and reference gene transcripts in 5 brain regions of 21, 8, and 13 deceased subjects with idiopathic PD, Lewy body dementia and controls without neurodegenerative disorders, respectively. We observed reductions of CNS-specific transcripts (encoding full-length isoforms) only in the substantia nigra pars compacta of PD and Lewy body dementia. However, in the substantia nigra and globus pallidus of PD cases we found an up-regulation of transcripts encoding the 17 kDa proteins that ...Continue Reading

Citations

Oct 8, 2020·Cells·Joseph M Chambers, Rebecca A Wingert
Nov 5, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Florian GeltingerMark Rinnerthaler
Apr 4, 2021·International Journal of Molecular Sciences·Elena PiccininGaetano Villani
Jun 15, 2021·ACS Chemical Neuroscience·Prabitha PB R Prashantha Kumar
Jul 17, 2021·Neural Regeneration Research·Jessica D PanesJorge Fuentealba
Sep 22, 2021·Molecular Neurobiology· Neha S, Pankaj Singh Dholaniya
Oct 16, 2021·Life Science Alliance·Oswaldo A LozoyaRichard P Woychik

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