Abstract:
Alzheimer\'s disease (AD) affects millions of people worldwide and is a gradually worsening neurodegenerative condition. The accumulation of abnormal proteins, such as tau and beta-amyloid, in the brain is a hallmark of AD pathology. 14-3-3 proteins have been implicated in AD pathology in several ways. One proposed mechanism is that 14-3-3 proteins interact with tau protein and modulate its phosphorylation, aggregation, and toxicity. Tau is a protein associated with microtubules, playing a role in maintaining the structural integrity of neuronal cytoskeleton. However, in the context of Alzheimer\'s disease (AD), an abnormal increase in its phosphorylation occurs. This leads to the aggregation of tau into neurofibrillary tangles, which is a distinctive feature of this condition. Studies have shown that 14-3-3 proteins can bind to phosphorylated tau and regulate its function and stability. In addition, 14-3-3 proteins have been shown to interact with beta-amyloid (Aβ), the primary component of amyloid plaques in AD. 14-3-3 proteins can regulate the clearance of Aβ through the lysosomal degradation pathway by interacting with the lysosomal membrane protein LAMP2A. Dysfunction of lysosomal degradation pathway is thought to contribute to the accumulation of Aβ in the brain and the progression of AD. Furthermore, 14-3-3 proteins have been found to be downregulated in the brains of AD patients, suggesting that their dysregulation may contribute to AD pathology. For example, decreased levels of 14-3-3 proteins in cerebrospinal fluid have been suggested as a biomarker for AD. Overall, these findings suggest that 14-3-3 proteins may play an important role in AD pathology and may represent a potential therapeutic target for the disease. However, further research is needed to fully understand the mechanisms underlying the involvement of 14-3-3 proteins in AD and to explore their potential as a therapeutic target.
摘要:
阿尔茨海默病(AD)影响全球数百万人,是一种逐渐恶化的神经退行性疾病。异常蛋白质的积累,如tau和β-淀粉样蛋白,在大脑中是AD病理学的标志。14-3-3蛋白以几种方式与AD病理学有关。一种提出的机制是14-3-3蛋白与tau蛋白相互作用并调节其磷酸化,聚合,和毒性。Tau是一种与微管相关的蛋白质,在维持神经元细胞骨架的结构完整性方面发挥作用。然而,在阿尔茨海默病(AD)的背景下,发生磷酸化异常增加。这导致tau聚集成神经原纤维缠结,这是这种情况的一个显著特征。研究表明,14-3-3蛋白可以与磷酸化tau结合并调节其功能和稳定性。此外,14-3-3蛋白已显示与β-淀粉样蛋白(Aβ)相互作用,AD中淀粉样蛋白斑的主要成分。14-3-3蛋白可以通过与溶酶体膜蛋白LAMP2A相互作用,通过溶酶体降解途径调节Aβ的清除。溶酶体降解途径的功能障碍被认为有助于Aβ在脑中的积累和AD的进展。此外,已发现14-3-3蛋白在AD患者的大脑中下调,提示它们的失调可能与AD病理有关。例如,脑脊液中14-3-3蛋白水平降低已被认为是AD的生物标志物。总的来说,这些发现提示14-3-3蛋白可能在AD病理中发挥重要作用,并可能成为该疾病的潜在治疗靶点.然而,需要进一步的研究来充分了解14-3-3蛋白参与AD的潜在机制,并探索其作为治疗靶点的潜力.