Thrombospondin-1 prevents amyloid beta mediated synaptic pathology in Alzheimer’s disease

Title
Thrombospondin-1 prevents amyloid beta mediated synaptic pathology in Alzheimer’s disease
Authors
류훈손성민남동우차문용김경호변자영묵인희
Keywords
TSP-1; Neuron-astrocyte crosstalk; Synaptic dysfunction; Ab; Alzheimer’s disease (AD)
Issue Date
2015-12
Publisher
Neurobiology of aging
Citation
VOL 36, NO 12-3227
Abstract
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 (Aβ), secreted TSP-1 was decreased in autophagy-dependent manner. In addition, treatment with Aβ induced synaptic pathology, such as decreased dendritic spine density and reduced synaptic activity. These effects were prevented by coincubation of TSP-1 with Aβ, 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 Aβ-mediated reduction of synaptic proteins and related signaling pathways. These results indicate that TSP-1 is a potential therapeutic target in AD pathogenesis.
URI
http://pubs.kist.re.kr/handle/123456789/64628
ISSN
0197-4580
Appears in Collections:
KIST Publication > Article
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