Pivotal roles of p62 and selective autophagy in tau deposition and consequent neurodegeneration revealed with tauopathy mouse models

在阿尔茨海默病中，异常tau蛋白产生的细胞毒性被认为是神经元死亡的主要原因之一。本研究的结果表明，选择性自噬和p62，一种介导选择性自噬的泛素化货物受体，密切参与异常tau蛋白引起的神经元死亡。p62通过消除非纤维状过度磷酸化的tau种类并将过度磷酸化的tau隔离到细胞体中来对tau病理发挥神经保护作用。此外，我们的研究结果表明，p62处理异常tau蛋白的能力不足会导致tau蛋白积累下的神经元死亡。

In Alzheimer’s disease, cytotoxicity exerted by abnormal tau is considered to be one of the main causes of neuronal death. Results from the present study indicate that selective autophagy and p62, a ubiquitinated cargo receptor mediating selective autophagy, are closely involved in neuronal death provoked by abnormal tau. p62 exerted neuroprotection against tau pathologies by eliminating nonfibrillar hyperphosphorylated tau species and sequestering hyperphosphorylated tau into cell bodies. Moreover, our findings suggested that insufficient capacity of p62 for processing of abnormal tau induces neuron death under tau accumulation.