College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
School of Health Sciences and Technology, University of Petroleum and Energy Studies, Bidholi, Dehradun, India.
Neurotox Res. 2023 Dec;41(6):698-707. doi: 10.1007/s12640-023-00670-3. Epub 2023 Oct 17.
Alzheimer's disease contributes to 60-70% of all dementia cases in the general population. Belonging to the BIN1/amphiphysin/RVS167 (BAR) superfamily, the bridging integrator (BIN1) has been identified to impact two major pathological hallmarks in Alzheimer's disease (AD), i.e., amyloid beta (Aβ) and tau accumulation. Aβ accumulation is found to increase by BIN1 knockdown in cortical neurons in late-onset AD, due to BACE1 accumulation at enlarged early endosomes. Two BIN1 mutants, KR and PL, were identified to exhibit Aβ accumulation. Furthermore, BIN1 deficiency by BIN1-related polymorphisms impairs the interaction with tau, thus elevating tau phosphorylation, altering synapse structure and tau function. Even though the precise role of BIN1 in the neuronal tissue needs further investigation, the authors aim to throw light on the potential of BIN1 and unfold its implications on tau and Aβ pathology, to aid AD researchers across the globe to examine BIN1, as an appropriate target gene for disease management.
阿尔茨海默病导致普通人群中 60-70%的痴呆病例。桥连整合因子(BIN1)属于 BIN1/ amphiphysin/RVS167(BAR)超家族,已被确定对阿尔茨海默病(AD)的两个主要病理标志有影响,即淀粉样β(Aβ)和 tau 积聚。由于晚期 AD 皮质神经元中的 BACE1 在扩大的早期内涵体中积聚,BIN1 敲低导致 Aβ 积聚增加。已经鉴定出两种 BIN1 突变体 KR 和 PL 表现出 Aβ 积聚。此外,BIN1 相关多态性导致 BIN1 缺乏会损害与 tau 的相互作用,从而提高 tau 磷酸化水平,改变突触结构和 tau 功能。尽管 BIN1 在神经元组织中的确切作用需要进一步研究,但作者旨在阐明 BIN1 的潜在作用,并阐明其对 tau 和 Aβ 病理学的影响,以帮助全球 AD 研究人员检查 BIN1,作为疾病管理的适当靶基因。