%0 Journal Article
%T Neuroprotection by Epigenetic Modulation in a Transgenic Model of Multiple System Atrophy
%A Edith Sturm
%A Florian Krismer
%A Gregor K. Wenning
%A Lisa Fellner
%A Nadia Stefanova
%A Werner Poewe
%J Archive of "Neurotherapeutics".
%D 2016
%R 10.1007/s13311-016-0447-1
%X Similar to Parkinson disease, multiple system atrophy (MSA) presents neuropathologically with nigral neuronal loss; however, the hallmark intracellular ¦Á-synuclein (¦ÁSyn) accumulation in MSA affects typically oligodendrocytes to form glial cytoplasmic inclusions. The underlying pathogenic mechanisms remain unclear. As MSA is predominantly sporadic, epigenetic mechanisms may play a role. We tested the effects of the pan-histone deacetylase inhibitor (HDACi) sodium phenylbutyrate in aged mice overexpressing ¦ÁSyn under the control of the proteolipid protein promoter (PLP¨C¦ÁSyn) designed to model MSA and characterized by ¦ÁSyn accumulation in oligodendrocytes and nigral neurodegeneration. HDACi improved motor behavior and survival of nigral neurons in PLP¨C¦ÁSyn mice. Furthermore, HDACi reduced the density of oligodendroglial ¦ÁSyn aggregates, which correlated with the survival of nigral neurons in PLP¨C¦ÁSyn mice. For the first time, we suggest a role of HDACi in the pathogenesis of MSA-like neurodegeneration and support the future development of selective HDACi for MSA therapy
%K ¦Á-Synuclein
%K nigral degeneration
%K phenylbutyrate
%K histone acetylation
%K neuroprotection
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081120/