{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:54:49Z","timestamp":1791302089496,"version":"4.1.0"},"reference-count":318,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder in the elderly, characterized by extracellular amyloid \u03b2\u2011 (A\u03b2) plaque deposition and intracellular neurofibrillary tangles (NFTs). Impaired autophagy, the cellular pathway for degrading damaged organelles and misfolded proteins, and cellular senescence, permanent cell cycle arrest with proinflammatory secretions, have emerged as key contributors to AD pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a narrative review of recent mechanistic and preclinical studies investigating (1) autophagic flux and its role in A\u03b2 and tau clearance; (2) the accumulation and secretory phenotype of senescent cells in the aging brain; (3) interactions between autophagy impairment and senescence; and (4) the efficacy of autophagy enhancers (e.g., rapamycin and metformin) and senolytic agents in rodent models of AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Defective autophagosome\u2013lysosome fusion in AD causes autophagic vacuole buildup with amyloid precursor protein and \u03b2\u2011secretase, boosting A\u03b2 generation and hindering tau clearance, promoting neurofibrillary tangles. In AD models, senescent neurons and microglia release pro\u2011inflammatory cytokines (SASP), fueling neuroinflammation and synaptic dysfunction. Decline in autophagy induces senescence and blocks clearance in a vicious cycle. Rapamycin and metformin restore autophagic flux, reduce A\u03b2 and tau pathologies, and improve memory. Senolytics clear senescent cells, reduce inflammation, and rescue cognition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Dysregulated autophagy and cellular senescence interact to drive the progression of AD. Targeting these pathways with autophagy\u2010boosting drugs and senolytic agents holds promise for disease\u2010modifying therapies aimed at halting or reversing neurodegeneration in Alzheimer's disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70503","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T05:35:42Z","timestamp":1753335342000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Autophagy and Cellular Senescence in Alzheimer's Disease: Key Drivers of Neurodegeneration"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3554-1750","authenticated-orcid":false,"given":"Md Sadique","family":"Hussain","sequence":"first","affiliation":[{"name":"Uttaranchal Institute of Pharmaceutical Sciences Uttaranchal University  Dehradun India"},{"name":"School of Pharmaceutical Sciences Lovely Professional University  Phagwara Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7575-3670","authenticated-orcid":false,"given":"Neetu","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Research GLA University  Mathura Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baby","family":"Ilma","sequence":"additional","affiliation":[{"name":"Sharda School of Pharmacy Sharda University  Greater Noida Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rekha","family":"M M","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, School of Sciences JAIN (Deemed to Be University)  Bangalore Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya Priyadarshini","family":"Nayak","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IMS and SUM Hospital Siksha \u2018O\u2019 Anusandhan (Deemed to Be University)  Bhubaneswar Odisha India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandeep","family":"Kaur","sequence":"additional","affiliation":[{"name":"Department of Allied Healthcare and Sciences Vivekananda Global University  Jaipur Rajasthan India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Khachi","sequence":"additional","affiliation":[{"name":"Department of Applied Sciences, Chandigarh Engineering College Chandigarh Group of Colleges\u2010Jhanjeri  Mohali Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavita","family":"Goyal","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Graphic Era (Deemed to Be University)  Dehradun India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arcot","family":"Rekha","sequence":"additional","affiliation":[{"name":"Dr.D.Y.Patil Medical College, Hospital and Research Centre  Pimpri, Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurabh","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Chameli Devi Institute of Pharmacy  Indore Madhya Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaurav","family":"Gupta","sequence":"additional","affiliation":[{"name":"Centre for Research Impact &amp; 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