Sharma Ravikant, Abubakar M D, Bisht Priya, Rachamalla Mahesh, Kumar Arun, Murti Krishna, Ravichandiran Velayutham, Kumar Nitesh
Research Institute of Biomedicine, University of Oulu, Aapistie 5, 90014 Oulu, Finland.
Department of Pharmacology and Toxicology, National Institution of Pharmaceutical Education and Research, Hajipur, Vaishali-844102, Bihar, India.
Curr Mol Pharmacol. 2023 Oct 25. doi: 10.2174/0118761429272806231020045840.
BACKGROUND: Arsenic is present in above permissible safe limits in groundwater, soil, and food, in various areas of the world. This is increasing exposure to humankind and affecting health in various ways. Alternation in cognition is one among them. Epidemiological research has reflected the impact of arsenic exposure on children in the form of diminished cognition. AIMS: Considering this fact, the present study reviewed the impact of arsenic on amyloid precursor protein, which is known to cause one of the commonest cognitive disorders such as Alzheimer's disease. METHODS: The present study reviews the arsenic role in the generation of amyloid-beta from its precursor that leads to Alzheimer's disease through the published article from Pubmed and Scopus. DESCRIPTION: According to the findings, regular, long-term exposure to arsenic beginning in infancy changes numerous arsenic level-regulating regions in the rat brain, which are related to cognitive impairments. Arsenic also affects the BBB clearance route by increasing RAGE expression. Arsenic triggers the proamyloidogenic pathway by increasing APP expression and subsequently, its processing by β-secretase and presenilin. Arsenic also affects mitochondrial dynamics, DNA repair pathway and epigenetic changes. The mechanism behind all these changes is explained in the present review article. CONCLUSION: A raised level of arsenic exposure affects the amyloid precursor protein, a factor for the early precipitation of Alzheimer's disease.
背景:在世界各个地区,地下水、土壤和食物中的砷含量超过了允许的安全限值。这增加了人类接触砷的机会,并以多种方式影响健康。认知改变就是其中之一。流行病学研究已经反映出砷暴露对儿童认知能力下降的影响。 目的:考虑到这一事实,本研究回顾了砷对淀粉样前体蛋白的影响,已知该蛋白会引发最常见的认知障碍之一,如阿尔茨海默病。 方法:本研究通过检索来自PubMed和Scopus的已发表文章,回顾了砷在其前体生成β-淀粉样蛋白过程中的作用,而β-淀粉样蛋白会导致阿尔茨海默病。 描述:根据研究结果,从婴儿期开始的长期、规律性砷暴露会改变大鼠大脑中许多与砷水平调节相关的区域,这些区域与认知障碍有关。砷还通过增加晚期糖基化终末产物受体(RAGE)的表达来影响血脑屏障清除途径。砷通过增加淀粉样前体蛋白(APP)的表达,随后通过β-分泌酶和早老素对其进行加工,从而触发淀粉样蛋白生成途径。砷还会影响线粒体动力学、DNA修复途径和表观遗传变化。本综述文章解释了所有这些变化背后的机制。 结论:砷暴露水平升高会影响淀粉样前体蛋白,而该蛋白是阿尔茨海默病早期发病的一个因素。
Curr Mol Pharmacol. 2023-10-25
IEEE J Transl Eng Health Med. 2025-4-10
2025-1
Psychopharmacol Bull. 2024-7-8
Cochrane Database Syst Rev. 2003
Cochrane Database Syst Rev. 2017-11-22
MedComm (2020). 2025-8-19
Mol Biol Rep. 2025-3-26
J Clin Med. 2024-4-19