Reversal of cognitive deficits in FUS^R521G amyotrophic lateral sclerosis mice by arimoclomol and a class I histone deacetylase inhibitor independent of heat shock protein induction.

ABSTRACT: Protein misfolding and mislocalization are common to both familial and sporadic forms of amyotrophic lateral sclerosis (ALS). Maintaining proteostasis through induction of heat shock proteins (HSP) to increase chaperoning capacity is a rational therapeutic strategy in the treatment of ALS. However, the threshold for upregulating stress-inducible HSPs remains high in neurons, presenting a therapeutic obstacle. This study used mouse models expressing the ALS variants FUS^R521G or SOD1^G93A to follow up on previous work in cultured motor neurons showing varied effects of the HSP co-inducer, arimoclomol, and class I histone deacetylase (HDAC) inhibitors on HSP expression depending on the ALS variant being expressed. As in cultured neurons, neither expression of the transgen

SUBMITTER: Pelaez MC 

PROVIDER: S-EPMC11579874 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature