Hook Proteins: Association with Alzheimer Pathology and Regulatory Role of Hook3 in Amyloid Beta Generation

Defects in intracellular transport are implicated in the pathogenesis of Alzheimer’s disease (AD). Hook proteins are a family of cytoplasmic linker proteins that participate in endosomal transport. In this study we show that Hook1 and Hook3 are expressed in neurons while Hook2 is predominantly expressed in astrocytes. Furthermore, Hook proteins are associated with pathological hallmarks in AD; Hook1 and Hook3 are localized to tau aggregates and Hook2 to glial components within amyloid plaques. Additionally, the expression of Hook3 is reduced in AD. Modelling of Hook3 deficiency in cultured cells leads to slowing of endosomal transport and increases β-amyloid production. We propose that Hook3 plays a role in pathogenic events exacerbating AD.细胞内运输缺陷与阿尔茨海默病（AD）的发病机制密切相关。Hook蛋白（Hook proteins）是一类参与内体运输的细胞质连接蛋白家族。本研究发现，Hook1与Hook3在神经元中表达，而Hook2主要在星形胶质细胞中表达。进一步而言，Hook蛋白与AD的病理特征存在关联：Hook1和Hook3定位于tau蛋白聚集体，Hook2则定位于淀粉样斑块内的胶质细胞组分。除此之外，AD患者体内Hook3的表达水平显著下调。在培养细胞中构建Hook3缺失模型，可导致内体运输速率减慢，并增加β淀粉样蛋白的生成。我们提出，Hook3参与了加重AD病情的致病过程。