Department of Neurology, National Reference Center for TSE, The German Center for Neurodegenerative Diseases (DZNE), Georg-August-University, University Medicine Gottingen, Goettingen, Germany.
National Center for Drug Research and Evaluation, Institute Superiore di Sanità, Rome, Italy.
Transl Neurodegener. 2023 Mar 14;12(1):12. doi: 10.1186/s40035-023-00342-4.
α-Synucleinopathies, such as Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy, are a class of neurodegenerative diseases exhibiting intracellular inclusions of misfolded α-synuclein (αSyn), referred to as Lewy bodies or oligodendroglial cytoplasmic inclusions (Papp-Lantos bodies). Even though the specific cellular distribution of aggregated αSyn differs in PD and DLB patients, both groups show a significant pathological overlap, raising the discussion of whether PD and DLB are the same or different diseases. Besides clinical investigation, we will focus in addition on methodologies, such as protein seeding assays (real-time quaking-induced conversion), to discriminate between different types of α-synucleinopathies. This approach relies on the seeding conversion properties of misfolded αSyn, supporting the hypothesis that different conformers of misfolded αSyn may occur in different types of α-synucleinopathies. Understanding the pathological processes influencing the disease progression and phenotype, provoked by different αSyn conformers, will be important for a personalized medical treatment in future.
α-突触核蛋白病，如帕金森病（PD）、路易体痴呆（DLB）和多系统萎缩，是一类具有细胞内错误折叠的α-突触核蛋白（αSyn）包涵体的神经退行性疾病，称为路易体或少突胶质细胞胞质包涵体（Papp-Lantos 体）。尽管 PD 和 DLB 患者中聚集的 αSyn 的特定细胞分布不同，但这两个组都表现出明显的病理重叠，引发了 PD 和 DLB 是否为同一种或不同疾病的讨论。除了临床研究，我们还将重点关注蛋白质接种测定（实时液滴动态转换）等方法，以区分不同类型的 α-突触核蛋白病。这种方法依赖于错误折叠的 αSyn 的接种转换特性，支持不同构象的错误折叠的 αSyn 可能存在于不同类型的 α-突触核蛋白病的假说。了解不同的 αSyn 构象对疾病进展和表型的病理过程的影响，对于未来的个性化医疗治疗将是重要的。
