Inhibition of nuclear-retained HDAC5 interactome prevents neurite degeneration induced by α-synuclein overexpression
Martina Mazzocchi, Louise M. Collins, Aideen M. Sullivan, Gerard W. O'Keeffe · FENS Forum 2024
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterised by midbrain dopaminergic neuron degeneration and intracellular a-synuclein (aSyn) accumulation. Here we show that AAV-shRNA-mediated inhibition of HDAC5 protected against aSyn-induced neurodegeneration in vitro and in vivo. We also show that AAV-mediated overexpression of aSyn induces HDAC5 nuclear accumulation in dopaminergic neurons in the rat substantia nigra in vivo, and in SH-SY5Y cells in vitro. To investigate the nuclear HDAC5 complex induced by aSyn, we used a co-immunoprecipitation proteomics approach t
ePoster · Neuroscience