Thrombospondin-1 protects against A?-induced mitochondrial fragmentation and dysfunction in hippocampal cells.

ABSTRACT: Alzheimer's disease (AD) is often characterized by the impairment of mitochondrial function caused by excessive mitochondrial fragmentation. Thrombospondin-1 (TSP-1), which is primarily secreted from astrocytes in the central nervous system (CNS), has been suggested to play a role in synaptogenesis, spine morphology, and synaptic density of neurons. In this study, we investigate the protective role of TSP-1 in the recovery of mitochondrial morphology and function in amyloid ? (A?)-treated mouse hippocampal neuroblastoma cells (HT22). We observe that TSP-1 inhibits A?-induced mitochondrial fission by maintaining phosphorylated-Drp1 (p-Drp1) levels, which results in reduced Drp1 translocation to the mitochondria. By using gabapentin, a drug that antagonizes the interaction between TSP-1 and its neuronal receptor ?2?1, we observe that ?2?1 acts as one of the target receptors for TSP-1, and blocks the reduction of the p-Drp1 to Drp1 ratio, in the presence of A?. Taken together, TSP-1 appears to contribute to maintaining the balance in mitochondrial dynamics and mitochondrial functions, which is crucial for neuronal cell viability. These data suggest that TSP-1 may be a potential therapeutic target for AD.

SUBMITTER: Kang S 

PROVIDER: S-EPMC5841271 | biostudies-other | 2018 Dec

REPOSITORIES: biostudies-other