Loss of function mutations in the gene PARK2, which encodes the protein parkin, cause autosomal recessive juvenile parkinsonism, a neurodegenerative disease characterized by degeneration of the dopaminergic neurons localized in the substantia nigra pars compacta. No therapy is effective in slowing disease progression mostly because the pathogenesis of the disease is yet to be understood. From accruing evidence suggesting that the protein parkin directly regulates synapses it can be hypothesized that PARK2 gene mutations lead to early synaptic damage that results in dopaminergic neuron loss over time. We review evidence that supports the role of parkin in modulating excitatory and dopaminergic synapse functions. We also discuss how these findings underpin the concept that autosomal recessive juvenile parkinsonism can be primarily a synaptopathy. Investigation into the molecular interactions between parkin and synaptic proteins may yield novel targets for pharmacologic interventions.

中文翻译：

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帕金森的突触功能

编码蛋白质parkin的基因PARK2中功能突变的丧失会导致常染色体隐性幼稚性帕金森病，这是一种神经退行性疾病，其特征是位于黑质致密部的多巴胺能神经元变性。没有疗法能有效地减缓疾病的进展，主要是因为尚未了解疾病的发病机理。根据越来越多的证据表明该蛋白帕金蛋白直接调节突触，可以假设PARK2基因突变导致早期的突触损伤，导致多巴胺能神经元随时间流逝。我们审查的证据支持在调节兴奋性和多巴胺能突触功能中帕金的作用。我们还讨论了这些发现如何支持常染色体隐性遗传性少年帕金森病可以主要是突触病的概念。对Parkin和突触蛋白之间的分子相互作用的研究可能会产生新的药理干预目标。