疾病
药物发现
神经科学
认知功能衰退
高磷酸化
阿尔茨海默病
药物开发
全基因组关联研究
生物
生物信息学
医学
药品
遗传学
痴呆
基因
激酶
药理学
病理
单核苷酸多态性
基因型
作者
Manish Kumar Singh,Yoonhwa Shin,Songhyun Ju,Sunhee Han,Sung Soo Kim,Insug Kang
摘要
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and affects millions of individuals globally. AD is associated with cognitive decline and memory loss that worsens with aging. A statistical report using U.S. data on AD estimates that approximately 6.9 million individuals suffer from AD, a number projected to surge to 13.8 million by 2060. Thus, there is a critical imperative to pinpoint and address AD and its hallmark tau protein aggregation early to prevent and manage its debilitating effects. Amyloid-β and tau proteins are primarily associated with the formation of plaques and neurofibril tangles in the brain. Current research efforts focus on degrading amyloid-β and tau or inhibiting their synthesis, particularly targeting APP processing and tau hyperphosphorylation, aiming to develop effective clinical interventions. However, navigating this intricate landscape requires ongoing studies and clinical trials to develop treatments that truly make a difference. Genome-wide association studies (GWASs) across various cohorts identified 40 loci and over 300 genes associated with AD. Despite this wealth of genetic data, much remains to be understood about the functions of these genes and their role in the disease process, prompting continued investigation. By delving deeper into these genetic associations, novel targets such as kinases, proteases, cytokines, and degradation pathways, offer new directions for drug discovery and therapeutic intervention in AD. This review delves into the intricate biological pathways disrupted in AD and identifies how genetic variations within these pathways could serve as potential targets for drug discovery and treatment strategies. Through a comprehensive understanding of the molecular underpinnings of AD, researchers aim to pave the way for more effective therapies that can alleviate the burden of this devastating disease.
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