The Role of Membrane Damage in Neurodegeneration

膜损伤被认为是阿尔茨海默病（AD）的早期致病事件。最近的全基因组关联研究（GWAS）已经确定了与迟发性阿尔茨海默病（LOAD）风险增加相关的三个广泛的细胞功能领域：内吞作用、磷脂代谢和先天免疫系统。总之，这些证明了膜完整性在AD中的重要性。运输所需的内体分选复合体（ESCRT）途径在介导膜修复中起重要作用，并与神经变性有关。CHMP2B （ESCRT复合物的一个组成部分）的突变导致一种罕见的额颞叶痴呆（FTD）。最近还发现了进一步的联系，即cd2相关蛋白（CD2AP）是LOAD的风险基因。CD2AP在细胞膜和肌动蛋白细胞骨架之间起作用，并通过ESCRT- i组分ALIX和TSG101与ESCRT复合物结合。

Membrane damage has been implicated as an early pathogenic event in Alzheimer's Disease (AD). Recent genome-wide association studies (GWAS) have identified three broad fields of cellular function associated with increased risk of late-onset Alzheimer's Disease (LOAD): endocytosis, phospholipid metabolism and the innate immune system. Together, these demonstrate the importance of membrane integrity in AD.The endosomal sorting complex required for transport (ESCRT) pathway has an essential role in mediating membrane repair and has been implicated in neurodegeneration. Mutations in CHMP2B, a component of ESCRT complexes, causes a rare type of frontotemporal dementia (FTD). A further link has also recently been recognized with the identification of CD2-associated protein (CD2AP) as a risk gene for LOAD. CD2AP functions between cell membranes and the actin cytoskeleton and binds to the ESCRT complex via the ESCRT-I components ALIX and TSG101.