Neuroprotection by ADAM10 inhibition requires TrkB signaling in the Huntington's disease hippocampus.

ABSTRACT: Synaptic dysfunction is an early pathogenic event leading to cognitive decline in Huntington's disease (HD). We previously reported that the active ADAM10 level is increased in the HD cortex and striatum, causing excessive proteolysis of the synaptic cell adhesion protein N-Cadherin. Conversely, ADAM10 inhibition is neuroprotective and prevents cognitive decline in HD mice. Although the breakdown of cortico-striatal connection has been historically linked to cognitive deterioration in HD, dendritic spine loss and long-term potentiation (LTP) defects identified in the HD hippocampus are also thought to contribute to the cognitive symptoms of the disease. The aim of this study is to investigate the contribution of ADAM10 to spine pathology and LTP defects of the HD hippocampus. We provide ev

SUBMITTER: Scolz A 

PROVIDER: S-EPMC11335257 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature