Publicación:
Vascular smooth muscle cell dysfunction contribute to neuroinflammation and Tau hyperphosphorylation in Alzheimer disease
Vascular smooth muscle cell dysfunction contribute to neuroinflammation and Tau hyperphosphorylation in Alzheimer disease
| dc.contributor.author | Aguilar-Pineda, Jorge A. | es_PE |
| dc.contributor.author | Vera-Lopez, Karin J. | es_PE |
| dc.contributor.author | Shrivastava, Pallavi | es_PE |
| dc.contributor.author | Chavez-Fumagalli, Miguel A. | es_PE |
| dc.contributor.author | Nieto-Montesinos, Rita | es_PE |
| dc.contributor.author | Alvarez-Fernandez, Karla L. | es_PE |
| dc.contributor.author | Goyzueta Mamani, Luis D. | es_PE |
| dc.contributor.author | Davila Del-Carpio, Gonzalo | es_PE |
| dc.contributor.author | Gomez-Valdez, Badhin | es_PE |
| dc.contributor.author | Miller, Clint L. | es_PE |
| dc.contributor.author | Malhotra, Rajeev | es_PE |
| dc.contributor.author | Lindsay, Mark E. | es_PE |
| dc.contributor.author | Lino Cardenas, Christian L. | es_PE |
| dc.date.accessioned | 2024-05-30T23:13:38Z | |
| dc.date.available | 2024-05-30T23:13:38Z | |
| dc.date.issued | 2021 | |
| dc.description | This research was funded by Consejo Nacional de Ciencia, Tecnologia e Innovacion Tecnologica de Peru (grant N~ 024-2019-Fondecyt-BM-INC.INV and CONCYTEC-FONDECYT-E038-01). | |
| dc.description.abstract | Despite the emerging evidence implying early vascular contributions to neurode-generative syndromes, the role of vascular smooth muscle cells (VSMCs) in the pathogenesis of Alzheimer disease (AD) is still not well understood. Herein, we show that VSMCs in brains of patients with AD and animal models of the disease are deficient in multiple VSMC contractile markers which correlated with Tau accumulation in brain arterioles. Ex vivo and in vitro experiments demonstrated that VSMCs undergo dramatic phenotypic transitions under AD-like conditions, adopting pro-inflammatory phenotypes. Notably, these changes coincided with Tau hyperphosphorylation at residues Y18, T205, and S262. We also observed that VSMC dysfunction occurred in an age-dependent manner and that expression of Sm22a protein was inversely correlated with CD68 and Tau expression in brain arterioles of the 3xTg-AD and 5xFAD mice. Together, these findings further support the contribution of dysfunctional VSMCs in AD pathogenesis and nominate VSMCs as a potential therapeutic target in AD. | |
| dc.description.sponsorship | Consejo Nacional de Ciencia, Tecnología e Innovación Tecnológica - Concytec | |
| dc.identifier.doi | https://doi.org/10.1016/j.isci.2021.102993 | |
| dc.identifier.uri | https://hdl.handle.net/20.500.12390/2951 | |
| dc.language.iso | eng | |
| dc.publisher | Cell Press | |
| dc.relation.ispartof | ISCIENCE | |
| dc.rights | info:eu-repo/semantics/openAccess | |
| dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject | Omics | |
| dc.subject | Molecular neuroscience | es_PE |
| dc.subject | Immunology | es_PE |
| dc.subject.ocde | https://purl.org/pe-repo/ocde/ford#3.02.25 | |
| dc.title | Vascular smooth muscle cell dysfunction contribute to neuroinflammation and Tau hyperphosphorylation in Alzheimer disease | |
| dc.type | info:eu-repo/semantics/article | |
| dspace.entity.type | Publication |