VPS10P (vacuolar protein sorting 10 protein) domain receptors are neuronal sorting receptors that direct cargo proteins to their destined location in subcellular compartments of the soma, dendrites, and the axon. Protein sorting by receptors such as SORLA, sortilin, and SorCS2 controls functional integrity and viability of neurons, whereas sorting receptor dysfunctions are linked to acute, psychiatric, and neurodegenerative diseases. Here, we discuss molecular mechanisms that define ligand repertoire and sorting path and that control plasticity of VPS10P domain receptor expression in the healthy brain and in response to injury. These findings highlight important concepts in neuronal protein sorting and why aberrant sorting contributes to the progression of devastating diseases of the human brain, including epilepsy, Alzheimer's disease, and frontotemporal dementia.

中文翻译：

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VPS10P 域受体：梳理大脑健康和疾病

VPS10P（液泡蛋白分选 10 蛋白）域受体是神经元分选受体，可将货物蛋白质引导至它们在体细胞、树突和轴突的亚细胞区室中的预定位置。SORLA、sortilin 和 SorCS2 等受体的蛋白质分选控制神经元的功能完整性和活力，而分选受体功能障碍与急性、精神疾病和神经退行性疾病有关。在这里，我们讨论了定义配体库和分类路径以及控制健康大脑中 VPS10P 结构域受体表达的可塑性和对损伤的反应的分子机制。这些发现突出了神经元蛋白质分类中的重要概念，以及为什么异常分类会导致人类大脑破坏性疾病的进展，包括癫痫、阿尔茨海默病、