HDAC6 and RhoA Are Novel Players in Abeta-driven Disruption of Neuronal Polarity

Overview

Journal Nat Commun

Specialty Biology

Date 2015 Jul 23

PMID 26198811

Citations 41

Authors

Hanako Tsushima

Marco Emanuele

Alice Polenghi

Alessandro Esposito

Massimo Vassalli

Andrea Barberis

Francesco Difato

Evelina Chieregatti

Affiliations

Soon will be listed here.

Abstract

Maintenance of neuronal polarity and regulation of cytoskeletal dynamics are vital during development and to uphold synaptic activity in neuronal networks. Here we show that soluble β-amyloid (Aβ) disrupts actin and microtubule (MT) dynamics via activation of RhoA and inhibition of histone deacetylase 6 (HDAC6) in cultured hippocampal neurons. The contact of Aβ with the extracellular membrane promotes RhoA activation, leading to growth cone collapse and neurite retraction, which might be responsible for hampered neuronal pathfinding and migration in Alzheimer's disease (AD). The inhibition of HDAC6 by Aβ increases the level of heterodimeric acetylated tubulin and acetylated tau, both of which have been found altered in AD. We also find that the loss of HDAC6 activity perturbs the integrity of axon initial segment (AIS), resulting in mislocalization of ankyrin G and increased MT instability in the AIS concomitant with loss of polarized localization of tau and impairment of action potential firing.

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