國家衛生研究院 NHRI:Item 3990099045/5441
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    题名: Mechanism mediating oligomeric A beta clearance by naive primary microglia
    其它题名: Mechanism mediating oligomeric Aβ clearance by naive primary microglia
    作者: Yang, CN;Shiao, YJ;Shie, FS;Guo, BS;Chen, PH;Cho, CY;Chen, YJ;Huang, FL;Tsay, HJ
    贡献者: Division of Mental Health and Addiction Medicine
    摘要: The accumulation of soluble oligomeric amyloid-β peptide (oAβ) proceeds the formation of senile plaques and contributes to synaptic and memory deficits in Alzheimer's disease (AD). The mechanism of mediating microglial oAβ :clearance remains unclear and thought to occur via scavenger receptors (SRs) in microglia. SRs respond to their ligands in a subtype-specific manner. Therefore, we sought to identify the specific subtypes of SRs that mediate oAβ :internalization and proteases that degrade oAβ :species in naive primary microglia. The component of oAβ species were characterized by western blot analysis, analytical ultracentrifugation analysis, and atomic force microscopy. The oAβ species remained soluble in the medium and microglial lysates during incubation at 37 °C. SR-A, but not CD36, mediated oAβ internalization in microglia as suggested by the use of subtype-specific neutralizing antibodies and small interfering RNAs (siRNAs). Immunoprecipitation analysis showed that oAβ :interacted with SR-A on the plasma membrane. After internalization, over 40% of oAβ vesicles were trafficked toward lysosomes and degraded by cysteine proteases, including cathepsin B. The inhibitors of proteasome, neprilysin, matrix metalloproteinases, and insulin degrading enzyme failed to protect internalized oAβ from degradation. Our study suggests that SR-A and lysosomal cathepsin B are critical in microglial oAβ :clearance, providing insight into how microglia are involved in the clearance of oAβ and their roles in the early stages of AD.
    日期: 2011-06
    關聯: Neurobiology of Disease. 2011 Jun;42(3):221-230.
    Link to: http://dx.doi.org/10.1016/j.nbd.2011.01.005
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0969-9961&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000290081700002
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=79954632126
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