Systemic overexpression of SQSTM1/p62 accelerates disease onset in a SOD1^H46R-expressing ALS mouse model.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by a selective loss of upper and lower motor neurons. Recent studies have shown that mutations in SQSTM1 are linked to ALS. SQSTM1 encodes SQSTM1/p62 that regulates not only autophagy via the association with MAP1LC3/LC3 and ubiquitinated proteins but also the KEAP1-NFE2L2/Nrf2 anti-oxidative stress pathway by interacting with KEAP1. Previously, we have demonstrated that loss of SQSTM1 exacerbates disease phenotypes in a SOD1^H46R-expressing ALS mouse model. To clarify the effects of SQSTM1 overexpression in this model, we generated SQSTM1 and SOD1 ^H46R double-transgenic (SQSTM1;SOD1 ^H46R ) mice. SQSTM1;SOD1 ^H46R mice exhibited earlier disease onset and sh

SUBMITTER: Mitsui S 

PROVIDER: S-EPMC5975400 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature