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ORIGINAL RESEARCH article

Front. Cell. Neurosci.
Sec. Non-Neuronal Cells
Volume 18 - 2024 | doi: 10.3389/fncel.2024.1453038
This article is part of the Research Topic The role of inflammatory processes in neurodegeneration: cellular, tissue and systemic mechanisms View all articles

Multifaceted Neuroprotective Approach of Trolox in Alzheimer's disease Mouse Model: Targeting Aβ Pathology, Neuroinflammation, Oxidative Stress, and Synaptic Dysfunction

Provisionally accepted
Muhammad Tahir Muhammad Tahir 1*Min H. Kang Min H. Kang 1*Tae J. Park Tae J. Park 2*Jawad Ali Jawad Ali 1Kyonghwan Choe Kyonghwan Choe 1,3*Jun S. Park Jun S. Park 1*Myeong Ok Kim Myeong Ok Kim 1*
  • 1 Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of Korea., Gyeongsang National University, Jinju, Republic of Korea
  • 2 Haemato-oncology/Systems Medicine Group, Paul O’Gorman Leukaemia Research Centre, Institute of Cancer Sciences, MVLS, University of Glasgow, U.K., University of Glasgow, Glasgow, Scotland, United Kingdom
  • 3 Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, 6229 ER Maastricht, Netherlands, Maastricht University, Maastricht, Netherlands

The final, formatted version of the article will be published soon.

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder pathologically characterized by the deposition of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs) in the brain. The accumulation of these aggregated proteins causes memory and synaptic dysfunction, neuroinflammation and oxidative stress. Current research study aimed to assess neuroprotective properties of vitamin E (VE) analog trolox in Aβ1-42-induced AD mouse model. Aβ1-42 5μL/5min/mouse) was injected intracerebroventricularly (i.c.v) into wild-type adult mice brain to induce AD-like neurotoxicity. For biochemical analysis, western blotting and confocal microscopy were performed. Remarkably, intraperitoneal (i.p) treatment of trolox (30 mg/kg/mouse for 2 weeks) reduced the AD pathology by reducing the expression of Aβ, phosphorylated tau (p-tau), and beta-site amyloid precursor protein cleaving enzyme1 (BACE1) in both cortex and hippocampus regions of mice brain. Furthermore, trolox-treatment decreased neuroinflammation by inhibiting Toll-like receptor 4 (TLR4), phosphorylated nuclear factor-κB (pNF-κB) and interleukin-1beta (IL-1β) and other inflammatory biomarkers of glial cells (Ionized calcium-binding adaptor molecule 1 (Iba1) and Glial fibrillary acidic protein (GFAP)). Moreover, trolox reduced oxidative stress by enhancing the expression of nuclear factor erythroid-related factor 2 (NRF2) and heme oxygenase 1 (HO1). Likewise, trolox-induced synaptic markers including synaptosomal associated protein 23 (SNAP23), synaptophysin (SYN), and post-synaptic density protein 95 (PSD-95), and memory functions in AD mice. Our findings could prove to be a useful and novel strategy for the investigation of new medications to treat AD-associated neurodegenerative diseases.

    Keywords: Alzheimer's disease (AD), amyloid beta-plaques (Aβ), Neurofibrillary tangles (NFTs), trolox, Neuroinflammation, oxidative stress and neurodegeneration

    Received: 22 Jun 2024; Accepted: 23 Aug 2024.

    Copyright: © 2024 Tahir, Kang, Park, Ali, Choe, Park and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Muhammad Tahir, Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of Korea., Gyeongsang National University, Jinju, Republic of Korea
    Min H. Kang, Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of Korea., Gyeongsang National University, Jinju, Republic of Korea
    Tae J. Park, Haemato-oncology/Systems Medicine Group, Paul O’Gorman Leukaemia Research Centre, Institute of Cancer Sciences, MVLS, University of Glasgow, U.K., University of Glasgow, Glasgow, G12 8QQ, Scotland, United Kingdom
    Kyonghwan Choe, Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of Korea., Gyeongsang National University, Jinju, Republic of Korea
    Jun S. Park, Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of Korea., Gyeongsang National University, Jinju, Republic of Korea
    Myeong Ok Kim, Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of Korea., Gyeongsang National University, Jinju, Republic of Korea

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