阿尔茨海默病遗传风险因素在突触功能障碍中的作用。

The role of genetic risk factors of Alzheimer's disease in synaptic dysfunction.

机构信息

Division of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Hong Kong Center for Neurodegenerative Diseases, Hong Kong Science Park, Hong Kong, China; Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research Institute, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen, Guangdong 518057, China.

出版信息

Semin Cell Dev Biol. 2023 Apr;139:3-12. doi: 10.1016/j.semcdb.2022.07.011. Epub 2022 Jul 30.

DOI:10.1016/j.semcdb.2022.07.011

PMID:35918217

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by the progressive deterioration of cognitive functions. Due to the extended global life expectancy, the prevalence of AD is increasing among aging populations worldwide. While AD is a multifactorial disease, synaptic dysfunction is one of the major neuropathological changes that occur early in AD, before clinical symptoms appear, and is associated with the progression of cognitive deterioration. However, the underlying pathological mechanisms leading to this synaptic dysfunction remains unclear. Recent large-scale genomic analyses have identified more than 40 genetic risk factors that are associated with AD. In this review, we discuss the functional roles of these genes in synaptogenesis and synaptic functions under physiological conditions, and how their functions are dysregulated in AD. This will provide insights into the contributions of these encoded proteins to synaptic dysfunction during AD pathogenesis.

摘要

阿尔茨海默病（AD）是一种神经退行性疾病，其特征是认知功能的进行性恶化。由于全球预期寿命的延长，AD 在全球老龄化人口中的患病率正在增加。虽然 AD 是一种多因素疾病，但突触功能障碍是 AD 早期发生的主要神经病理学变化之一，早于临床症状出现，并与认知恶化的进展有关。然而，导致这种突触功能障碍的潜在病理机制尚不清楚。最近的大规模基因组分析已经确定了 40 多个与 AD 相关的遗传风险因素。在这篇综述中，我们讨论了这些基因在生理条件下参与突触发生和突触功能的作用，以及它们在 AD 中的功能失调情况。这将为这些编码蛋白在 AD 发病机制中对突触功能障碍的贡献提供深入了解。