{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:29:46Z","timestamp":1792045786667,"version":"4.4.0"},"reference-count":76,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T00:00:00Z","timestamp":1702512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Alzheimer\u2019s Association","award":["AARG-20-685663"],"award-info":[{"award-number":["AARG-20-685663"]}]},{"name":"Alzheimer\u2019s Association","award":["NIH R01NS104127"],"award-info":[{"award-number":["NIH R01NS104127"]}]},{"name":"Alzheimer\u2019s Association","award":["R01AG062572"],"award-info":[{"award-number":["R01AG062572"]}]},{"name":"Pennsylvania Department of Health Collaborative Research on Alzheimer\u2019s Disease (PA Cure)","award":["AARG-20-685663"],"award-info":[{"award-number":["AARG-20-685663"]}]},{"name":"Pennsylvania Department of Health Collaborative Research on Alzheimer\u2019s Disease (PA Cure)","award":["NIH R01NS104127"],"award-info":[{"award-number":["NIH R01NS104127"]}]},{"name":"Pennsylvania Department of Health Collaborative Research on Alzheimer\u2019s Disease (PA Cure)","award":["R01AG062572"],"award-info":[{"award-number":["R01AG062572"]}]},{"name":"Karen Toffler Charitable Trust","award":["AARG-20-685663"],"award-info":[{"award-number":["AARG-20-685663"]}]},{"name":"Karen Toffler Charitable Trust","award":["NIH R01NS104127"],"award-info":[{"award-number":["NIH R01NS104127"]}]},{"name":"Karen Toffler Charitable Trust","award":["R01AG062572"],"award-info":[{"award-number":["R01AG062572"]}]},{"name":"Lemole Center for Integrated Lymphatics research","award":["AARG-20-685663"],"award-info":[{"award-number":["AARG-20-685663"]}]},{"name":"Lemole Center for Integrated Lymphatics research","award":["NIH R01NS104127"],"award-info":[{"award-number":["NIH R01NS104127"]}]},{"name":"Lemole Center for Integrated Lymphatics research","award":["R01AG062572"],"award-info":[{"award-number":["R01AG062572"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Amyloid beta (A\u03b2) deposition within the brain vasculature is an early hallmark of Alzheimer\u2019s disease (AD), which triggers loss of brain vascular smooth muscle cells (BVSMCs) in cerebral arteries, via poorly understood mechanisms, altering cerebral blood flow, brain waste clearance, and promoting cognitive impairment. We have previously shown that, in brain endothelial cells (ECs), vasculotropic A\u03b2 species induce apoptosis through death receptors (DRs) DR4 and DR5 and mitochondria-mediated mechanisms, while FDA-approved carbonic anhydrase inhibitors (CAIs) prevent mitochondria-mediated EC apoptosis in vitro and in vivo. In this study, we analyzed A\u03b2-induced extrinsic and intrinsic (DR- and mitochondria-mediated) apoptotic pathways in BVSMC, aiming to unveil new therapeutic targets to prevent BVSMC stress and death. We show that both apoptotic pathways are activated in BVSMCs by oligomeric A\u03b242 and A\u03b240-Q22 (A\u03b2Q22) and mitochondrial respiration is severely impaired. Importantly, the CAIs methazolamide (MTZ) and acetazolamide (ATZ) prevent the pro-apoptotic effects in BVSMCs, while reducing caspase 3 activation and A\u03b2 deposition in the arterial walls of TgSwDI animals, a murine model of cerebral amyloid angiopathy (CAA). This study reveals new molecular targets and a promising therapeutic strategy against BVSMC dysfunction in AD, CAA, and ARIA (amyloid-related imaging abnormalities) complications of recently FDA-approved anti-A\u03b2 antibodies.<\/jats:p>","DOI":"10.3390\/cells12242840","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T06:53:16Z","timestamp":1702623196000},"page":"2840","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Amyloid Beta Oligomers Activate Death Receptors and Mitochondria-Mediated Apoptotic Pathways in Cerebral Vascular Smooth Muscle Cells; Protective Effects of Carbonic Anhydrase Inhibitors"],"prefix":"10.3390","volume":"12","author":[{"given":"Amy","family":"Anzovino","sequence":"first","affiliation":[{"name":"Alzheimer\u2019s Center at Temple, Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, 3500 N Broad St, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Canepa","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Center at Temple, Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, 3500 N Broad St, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micaelly","family":"Alves","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Center at Temple, Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, 3500 N Broad St, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole L.","family":"Lemon","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Center at Temple, Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, 3500 N Broad St, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana O.","family":"Carare","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2047-222X","authenticated-orcid":false,"given":"Silvia","family":"Fossati","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Center at Temple, Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, 3500 N Broad St, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.jacc.2019.10.062","article-title":"Alzheimer\u2019s Disease and Vascular Aging: JACC Focus Seminar","volume":"75","author":"Iadecola","year":"2020","journal-title":"J. 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