Son, Sung Min Nam, Dong Woo Cha, Moon-Yong Kim, Kyung Ho Byun, Jayoung Ryu, Hoon Mook-Jung, Inhee 2024-01-20T05:32:34Z 2024-01-20T05:32:34Z 2021-09-03 2015-12 0197-4580 https://pubs.kist.re.kr/handle/201004/124707 Alzheimer's disease (AD) is characterized by impaired cognitive function and memory loss, which are often the result of synaptic pathology. Thrombospondin (TSP) is an astrocyte-secreted protein, well known for its function as a modulator of synaptogenesis and neurogenesis. Here, we investigated the effects of TSP-1 on AD pathogenesis. We found that the level of TSP-1 expression was decreased in AD brains. When we treated astrocytes with amyloid beta (A beta), secreted TSP-1 was decreased in autophagy-dependent manner. In addition, treatment with Ab induced synaptic pathology, such as decreased dendritic spine density and reduced synaptic activity. These effects were prevented by coincubation of TSP-1 with A beta, which acts through the TSP-1 receptor alpha-2-delta-1 in neurons. Finally, intrasubicular injection with TSP-1 into AD model mouse brains mitigated the A beta-mediated reduction of synaptic proteins and related signaling pathways. These results indicate that TSP-1 is a potential therapeutic target in AD pathogenesis. (C) 2015 Elsevier Inc. All rights reserved. English ELSEVIER SCIENCE INC ASTROCYTE-SECRETED PROTEINS CENTRAL-NERVOUS-SYSTEM HIPPOCAMPAL-NEURONS NEURITE OUTGROWTH TRANSGENIC MICE FRONTAL-CORTEX CELL BIOLOGY GLIAL-CELLS BRAIN IDENTIFICATION Thrombospondin-1 prevents amyloid beta-mediated synaptic pathology in Alzheimer's disease Article 10.1016/j.neurobiolaging.2015.09.005 1 NEUROBIOLOGY OF AGING, v.36, no.12, pp.3214 - 3227 NEUROBIOLOGY OF AGING 36 12 3214 3227 scie scopus 000364676800010 2-s2.0-84946594819 Geriatrics & Gerontology Neurosciences Geriatrics & Gerontology Neurosciences & Neurology Article ASTROCYTE-SECRETED PROTEINS CENTRAL-NERVOUS-SYSTEM HIPPOCAMPAL-NEURONS NEURITE OUTGROWTH TRANSGENIC MICE FRONTAL-CORTEX CELL BIOLOGY GLIAL-CELLS BRAIN IDENTIFICATION TSP-1 Neuron-astrocyte crosstalk Synaptic dysfunction A beta Alzheimer&apos s disease (AD)