■液泡蛋白分选35(VPS35)在逆转录复合物中至关重要,控制细胞内的跨膜蛋白运输,它的功能障碍与神经退行性疾病有关。一种错觉突变,Asp620Asn(D620N),特别与家族性迟发性帕金森氏症有关,虽然在阿尔茨海默氏症中观察到VPS35水平降低,肌萎缩侧索硬化(ALS),额颞叶痴呆(FTD),和tau蛋白病。VPS35在某些神经元发育过程中的缺失可以引发神经变性,强调它对神经健康的必要性。目前的治疗研究主要针对有害蛋白质聚集体的清除和症状管理。针对VPS35的创新治疗方法正在研究中,尽管充分了解机制和最佳目标策略仍然是一个挑战。
■此评论提供了VPS35发现的详细信息,它在神经退行性机制中的作用——特别是在帕金森氏症和阿尔茨海默氏症中——及其与其他疾病的联系。它照亮了对VPS35在发展中的功能的最新见解,疾病,作为治疗靶点。
■VPS35是细胞功能和疾病关联的组成部分,使其成为开发疗法的重要候选人。调节VPS35活性的进展可能导致突破性治疗,不仅减缓疾病进展,而且还可能作为神经变性风险的生物标志物,标志着在管理这些复杂条件方面向前迈出了一步。
UNASSIGNED: Vacuolar Protein Sorting 35 (VPS35) is pivotal in the retromer complex, governing transmembrane protein trafficking within cells, and its dysfunction is implicated in neurodegenerative diseases. A missense mutation, Asp620Asn (D620N), specifically ties to familial late-onset Parkinson\'s, while reduced VPS35 levels are observed in Alzheimer\'s, amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and tauopathies. VPS35\'s absence in certain neurons during development can initiate neurodegeneration, highlighting its necessity for neural health. Present therapeutic research mainly targets the clearance of harmful protein aggregates and symptom management. Innovative treatments focusing on VPS35 are under investigation, although fully understanding the mechanisms and optimal targeting strategies remain a challenge.
UNASSIGNED: This review offers a detailed account of VPS35\'s discovery, its role in neurodegenerative mechanisms - especially in Parkinson\'s and Alzheimer\'s - and its link to other disorders. It shines alight on recent insights into VPS35\'s function in development, disease, and as a therapeutic target.
UNASSIGNED: VPS35 is integral to cellular function and disease association, making it a significant candidate for developing therapies. Progress in modulating VPS35\'s activity may lead to breakthrough treatments that not only slow disease progression but may also act as biomarkers for neurodegeneration risk, marking a step forward in managing these complex conditions.