Neuroprotection by Epigenetic Modulation in a Transgenic Model of Multiple System AtrophyReportar como inadecuado




Neuroprotection by Epigenetic Modulation in a Transgenic Model of Multiple System Atrophy - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Neurotherapeutics

, Volume 13, Issue 4, pp 871–879

First Online: 03 June 2016

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 the density of oligodendroglial αSyn aggregates, which correlated with the survival of nigral neurons in PLP–αSyn 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.

Key Wordsα-Synuclein nigral degeneration phenylbutyrate histone acetylation neuroprotection Electronic supplementary materialThe online version of this article doi:10.1007-s13311-016-0447-1 contains supplementary material, which is available to authorized users.

Download fulltext PDF



Autor: Edith Sturm - Lisa Fellner - Florian Krismer - Werner Poewe - Gregor K. Wenning - Nadia Stefanova

Fuente: https://link.springer.com/article/10.1007/s13311-016-0447-1







Documentos relacionados