{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:03:56Z","timestamp":1790287436603,"version":"4.1.0"},"reference-count":154,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T00:00:00Z","timestamp":1721260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Neurological Disorder Research Program of the \u201cNational Research Foundation (NRF)\u201d","award":["2020M3E5D9080660"],"award-info":[{"award-number":["2020M3E5D9080660"]}]},{"name":"Korean Government (MSIT)","award":["2020M3E5D9080660"],"award-info":[{"award-number":["2020M3E5D9080660"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a progressive neurodegenerative disorder that comprises amyloid-beta protein (A\u03b2) as a main component of neuritic plaques. Its deposition is considered a trigger for AD pathogenesis, progression, and the clinical symptoms of cognitive impairment. Some distinct pathological features of AD include phosphorylation of tau protein, oxidative stress, and mitochondrial dysfunction. These pathological consequences tend to produce reactive oxygen species (ROS), resulting in the dysregulation of various signaling pathways of neuroinflammation and neurodegeneration. The relationship between the A\u03b2 cascade and oxidative stress in AD pathogenesis is like a \u201cchicken and egg\u201d story, with the etiology of the disease regarding these two factors remaining a question of \u201cwhich comes first.\u201d However, in this review, we have tried our best to clarify the interconnection between these two mechanisms and to show the precise cause-and-effect relationship. Based on the above hallmarks of AD, several therapeutic strategies using natural antioxidants, monoclonal antibodies, and vaccines are employed as anti-A\u03b2 therapy to decrease ROS, A\u03b2 burden, chronic neuroinflammation, and synaptic failure. These natural antioxidants and immunotherapeutics have demonstrated significant neuroprotective effects and symptomatic relief in various in vitro and in vivo models, as well as in clinical trials for AD. However, none of them have received final approval to enter the drug market for mitigating AD. In this review, we extensively elaborate on the pitfalls, assurances, and important crosstalk between oxidative stress and A\u03b2 concerning current anti-A\u03b2 therapy. Additionally, we discuss future strategies for the development of more A\u03b2-targeted approaches and the optimization of AD treatment and mitigation.<\/jats:p>","DOI":"10.3390\/antiox13070862","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T16:51:12Z","timestamp":1721321472000},"page":"862","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["The Interplay of Protein Aggregation, Genetics, and Oxidative Stress in Alzheimer\u2019s Disease: Role for Natural Antioxidants and Immunotherapeutics"],"prefix":"10.3390","volume":"13","author":[{"given":"Jawad","family":"Ali","sequence":"first","affiliation":[{"name":"Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyonghwan","family":"Choe","sequence":"additional","affiliation":[{"name":"Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of Korea"},{"name":"Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Sung","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6394-3637","authenticated-orcid":false,"given":"Hyun Young","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Department of Pediatrics, Maastricht University Medical Center (MUMC+), 6202 AZ Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heeyoung","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Gyeongsang National University Hospital & College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Ju","family":"Park","sequence":"additional","affiliation":[{"name":"Haemato-Oncology\/Systems Medicine Group, Paul O\u2019Gorman Leukaemia Research Centre, Institute of Cancer Sciences, College of Medical, Veterinary & Life Sciences (MVLS), University of Glasgow, Glasgow G12 0ZD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myeong Ok","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of Korea"},{"name":"Alz-Dementia Korea Co., Jinju 52828, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1046\/j.1471-4159.1999.0730443.x","article-title":"Alzheimer\u2019s disease and the amyloid \u03b2 protein: What is the role of amyloid?","volume":"73","author":"Small","year":"1999","journal-title":"J. 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