PDF(Pubmed)
Abstract：
Parkinson\'s disease (PD) is clinically, pathologically, and genetically heterogeneous, resisting distillation to a single, cohesive disorder. Instead, each affected individual develops a virtually unique form of Parkinson\'s syndrome. Clinical manifestations consist of variable motor and nonmotor features, and myriad overlaps are recognized with other neurodegenerative conditions. Although most commonly characterized by alpha-synuclein protein pathology throughout the central and peripheral nervous systems, the distribution varies and other pathologies commonly modify PD or trigger similar manifestations. Nearly all PD is genetically influenced. More than 100 genes or genetic loci have been identified, and most cases likely arise from interactions among many common and rare genetic variants. Despite its complex architecture, insights from experimental genetic dissection coalesce to reveal unifying biological themes, including synaptic, lysosomal, mitochondrial, andimmune-mediated mechanisms of pathogenesis. This emerging understanding of Parkinson\'s syndrome, coupled with advances in biomarkers and targeted therapies, presages successful precision medicine strategies.
摘要：
帕金森病(PD)在临床上,病理上,和遗传异质性，抵抗蒸馏到一个单一的，凝聚力障碍。相反，每个受影响的个体都会发展出一种几乎独特的帕金森综合征。临床表现包括可变运动和非运动特征，和无数的重叠被认为与其他神经退行性疾病。尽管最常见的特征是整个中枢神经系统和周围神经系统的α-突触核蛋白蛋白病理学，分布不同，其他病理通常会改变PD或引发类似的表现。几乎所有PD都受遗传影响。已经确定了100多个基因或遗传基因座，大多数病例可能来自许多常见和罕见的遗传变异之间的相互作用。尽管架构复杂,从实验性基因解剖中获得的见解结合起来，揭示出统一的生物学主题，包括突触，溶酶体,线粒体，免疫介导的发病机制。对帕金森综合征的新认识,再加上生物标志物和靶向治疗的进展，预示着成功的精准医学策略。
