7-days of FREE Audio papers, translation & more with Prime
7-days of FREE Prime access
7-days of FREE Audio papers, translation & more with Prime
7-days of FREE Prime access
https://doi.org/10.1016/j.neurobiolaging.2020.02.001
Copy DOIJournal: Neurobiology of Aging | Publication Date: Feb 13, 2020 |
Citations: 23 |
Defective immune cell-mediated clearance of amyloid-beta (Aβ) and Aβ-associated inflammatory activation of immune cells are key contributors in pathogenesis of Alzheimer's disease (AD). However, the underlying mechanisms remain elusive. Shank-associated RH domain-interacting protein (SHARPIN) is a critical regulator of inflammatory response. Using in vitro cultures of THP-1-derived macrophages exposed to Aβ and AD patient–derived macrophages, we demonstrate the role of SHARPIN as an obligate regulator of Aβ phagocytosis and inflammation in macrophages. Specifically, Aβ-stimulated SHARPIN in THP-1 macrophages promoted Aβ phagocytosis and expression of proinflammatory markers. In addition, Aβ-stimulated SHARPIN in macrophages promoted neuronal cell-death in differentiated SHSY5Y neurons. Furthermore, we report a novel regulatory link between SHARPIN and the NLRP3 inflammasome in response to Aβ in THP-1 macrophages. In line with our in vitro observations, a strong positive association was demonstrated between levels of Aβ42 in blood plasma of mild cognitive impairment and AD patients with SHARPIN expression in macrophages obtained from respective patient-derived peripheral blood mononuclear cells. Together, our findings show SHARPIN as a critical determinant in mediating macrophage response to Aβ and pathogenesis of AD.
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.