TIMP-1 enhances Akt and BDNF signaling in neurons to reduce synaptic and cognitive deficits in 5xFAD mouse model of Alzheimer's disease.

ABSTRACT: Glial-secreted molecules influence neuronal function in Alzheimer's disease (AD), but their mechanisms of action are partially understood. Anti-inflammatory cytokine tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) is secreted by astrocytes early in response to amyloid-β and is suggested to have a neuroprotective function. We demonstrated that TIMP-1 levels are increased in 7-day-old 5xFAD versus wild-type mice but are drastically decreased from two months onwards. Administration of TIMP-1 protein in 5xFAD mice ameliorated AD-associated cognitive impairments. TIMP-1 regulated both neuronal apoptosis and autophagy by binding to CD63 receptors in an AD model. Synaptosomal and electrophysiological studies revealed that TIMP-1 reduces AD-related synaptic deficits, likely by promoting po

SUBMITTER: Sarkar S 

PROVIDER: S-EPMC12362966 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature