{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["4"],"submitter":["Kang S"],"pubmed_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 β (Aβ)-treated mouse hippocampal neuroblastoma cells (HT22). We observe that TSP-1 inhibits Aβ-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 α2δ1, we observe that α2δ1 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 Aβ. 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."],"journal":["Cell death discovery"],"pagination":["31"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5841271"],"repository":["biostudies-literature"],"pubmed_title":["Thrombospondin-1 protects against Aβ-induced mitochondrial fragmentation and dysfunction in hippocampal cells."],"pmcid":["PMC5841271"],"pubmed_authors":["Mook-Jung I","Byun J","Kang S","Son SM"],"additional_accession":[]},"is_claimable":false,"name":"Thrombospondin-1 protects against Aβ-induced mitochondrial fragmentation and dysfunction in hippocampal cells.","description":"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 β (Aβ)-treated mouse hippocampal neuroblastoma cells (HT22). We observe that TSP-1 inhibits Aβ-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 α2δ1, we observe that α2δ1 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 Aβ. 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.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Dec","modification":"2025-04-04T19:47:00.267Z","creation":"2019-03-26T23:12:26Z"},"accession":"S-EPMC5841271","cross_references":{"pubmed":["29531828"],"doi":["10.1038/s41420-017-0023-4"]}}