α-synuclein (αSyn) still remains a mysterious protein even two decades after SNCA encoding it was identified as the first causative gene of familial Parkinson's disease (PD). Accumulation of αSyn causes α-synucleinopathies including PD, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Recent advances in therapeutic approaches offer new antibody-, vaccine-, antisense-oligonucleotide- and small molecule-based options to reduce αSyn protein levels and aggregates in patient's brain. Gathering research information of other neurological disease particularly Alzheimer's disease, recent disappointment of an experimental amyloid plaques busting antibody in clinical trials underscores the difficulty of treating people who show even mild dementia as damage in their brain may already be too extensive. Prodromal intervention to inhibit the accumulation of pathogenic protein may advantageously provide a better outcome. However, treatment prior to onset is not ethically justified as standard practice at present. In this review, we initiate a refined concept to define early pathogenic state of αSyn accumulation before occurrence of brain damage as a disease criterion for αSyn dysregulation disease.

即使在SNCA编码被确认为家族性帕金森氏病（PD）的第一个致病基因后的二十年，α-突触核蛋白（αSyn）仍然仍然是一种神秘的蛋白质。αSyn的积累会引起α-突触核蛋白病，包括PD，路易体痴呆（DLB）和多系统萎缩（MSA）。治疗方法的最新进展提供了新的基于抗体，疫苗，反义寡核苷酸和小分子的选择，以降低患者大脑中αSyn蛋白的水平和聚集。收集其他神经系统疾病（尤其是阿尔茨海默氏病）的研究信息，最近在临床试验中对实验性淀粉样斑块破坏抗体的失望表明，很难治疗那些甚至表现出轻度痴呆的人，因为他们的大脑损害可能已经太广泛了。前驱干预抑制病原蛋白的积累可能有利地提供更好的结果。然而，目前尚无在伦理上证明发病前的治疗方法为标准的实践。在这篇综述中，我们提出了一个完善的概念，以将脑损伤发生之前αSyn积累的早期致病状态定义为αSyn失调性疾病的疾病标准。