Neuroprotection by Epigenetic Modulation in a Transgenic Model of Multiple System Atrophy.

ABSTRACT: Similar to Parkinson disease, multiple system atrophy (MSA) presents neuropathologically with nigral neuronal loss; however, the hallmark intracellular α-synuclein (αSyn) 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 αSyn under the control of the proteolipid protein promoter (PLP-αSyn) designed to model MSA and characterized by αSyn accumulation in oligodendrocytes and nigral neurodegeneration. HDACi improved motor behavior and survival of nigral neurons in PLP-αSyn mice. Furthermore, HDACi reduced th

SUBMITTER: Sturm E 

PROVIDER: S-EPMC5081120 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature