{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:57:23Z","timestamp":1790189843087,"version":"4.1.0"},"reference-count":193,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2020-NR049589"],"award-info":[{"award-number":["RS-2020-NR049589"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-00555975"],"award-info":[{"award-number":["RS-2025-00555975"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002631","name":"Gachon University","doi-asserted-by":"publisher","award":["GCU-202206050001"],"award-info":[{"award-number":["GCU-202206050001"]}],"id":[{"id":"10.13039\/501100002631","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) Alzheimer\u2019s disease (AD) is a progressive neurodegenerative disorder marked by protein aggregation, oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation, leading to cognitive decline. Current therapies remain largely symptomatic, highlighting the need for multi-target therapeutic strategies. Recent advances in antioxidant natural compounds and targeted protein degradation (TPD) technologies\u2014particularly proteolysis-targeting chimeras (PROTACs), offer complementary mechanisms for disease modification. Natural antioxidants, including flavonoids, polyphenols, terpenoids, and alkaloids, confer neuroprotection by reducing reactive oxygen species, activating Nrf2 pathways, restoring mitochondrial function, and suppressing neuroinflammation. PROTACs, in contrast, selectively degrade pathological proteins such as hyperphosphorylated tau, amyloid-\u03b2, and APP fragments through the ubiquitin\u2013proteasome system. The integrated \u201cAntiox-PROTAC\u201d approach combines these modalities to simultaneously mitigate oxidative stress and eliminate neurotoxic proteins. Natural compounds may act as warheads or scaffolds in PROTAC design, retaining antioxidant activity while enabling targeted degradation. Early preclinical findings demonstrate synergistic neuroprotective potential, though translational challenges remain, including blood\u2013brain barrier permeability, bioavailability, and delivery optimization. Future directions involve hybrid molecules, nanoparticle-based delivery, and personalized therapeutic strategies. Overall, the Antiox-PROTAC paradigm represents a next-generation, multi-modal framework with the potential to modify disease progression and enhance cognitive outcomes in Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.3390\/antiox14121426","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T16:31:52Z","timestamp":1764261112000},"page":"1426","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Antioxidant Natural Compounds Integrated with Targeted Protein Degradation: A Multi-Modal Strategy for Alzheimer\u2019s Disease Therapy"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2967-8838","authenticated-orcid":false,"given":"Desh Deepak","family":"Singh","sequence":"first","affiliation":[{"name":"Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur 303002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1102-1993","authenticated-orcid":false,"given":"Dharmendra Kumar","family":"Yadav","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Gachon University, Hambakmoeiro 191, Yeonsu-gu, Incheon 21924, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2510-3025","authenticated-orcid":false,"given":"Dongyun","family":"Shin","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Gachon University, Hambakmoeiro 191, Yeonsu-gu, Incheon 21924, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e70235","DOI":"10.1002\/alz.70235","article-title":"2025 Alzheimer\u2019s Disease Facts and Figures","volume":"21","author":"Gaugler","year":"2025","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"102199","DOI":"10.1016\/j.arr.2024.102199","article-title":"Recent Trends in Treatment Strategies for Alzheimer\u2019s Disease and the Challenges: A Topical Advancement","volume":"94","author":"Liu","year":"2024","journal-title":"Ageing Res. 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