Unveiling the cytoplasmic functions of HDAC4 in dystrophic skeletal muscle (DFM.AD004.310)

Area tematica

Scienze fisiche e tecnologie della materia

Area progettuale

Struttura responsabile del progetto di ricerca

Istituto di Nanotecnologia (NANOTEC)

Responsabile di progetto

VIVIANA MORESI
Telefono: 3381103030
E-mail: VIVIANA.MORESI@CNR.IT

Abstract

This proposal aims to define the non-nuclear functions of, Histone Deacetylase 4 (HDAC4), a factor likely
playing a role in skeletal muscle of mice affected by Duchenne Muscular Dystrophy. The latter is a genetic,
lethal pathology characterized by the progressive loss of skeletal muscle tissue, due to muscle fiber death
combined with the decrease in the muscle's ability to repair. Unfortunately, to date, there is no effective cure.
From our preliminary data, HDAC4 plays an unexpected role in the cytoplasm of dystrophic muscles in
mice, by regulating both muscle fragility and regeneration. We propose to identify the signals controlled by
HDAC4 in dystrophic muscles, with the final aim to propose new therapeutic approaches for the treatment of
Duchenne Muscular Dystrophy

Obiettivi

The scientific objective of this application is to define HDAC4 cytoplasmic functions in dystrophic skeletal
muscles, with the final aim to identify more specific therapeutic approaches to ameliorate muscular
dystrophy. HDAC4 intracellular localization will be deeply analyzed by live imaging in control and
mdx muscles, upon mechanical stretch. HDAC4 signaling and cytoplasmic partners will be identified
by proteomic analyses and validated by means of loss and gain-of-function models, stimulated emission
depletion (sted) microscopy and biochemical assays. Moreover, we plan to assess if HDAC4 cytoplasmic
functions depend on its deacetylase activity, by generating and over-expressing two mutant forms of HDAC4.

Data inizio attività

01/11/2021

Parole chiave

DMD, HDACi, HDAC4

Ultimo aggiornamento: 13/12/2024