Alpha-synuclein in Parkinson’s Disease and Synucleinopathies: Biology, Pathogenic Mechanisms, and Clinical Relevance

Alpha-synuclein (a-synuclein) research is at the forefront of neurodegenerative disease investigation, especially in the context of Parkinson’s disease (PD) and other synucleinopathies. The abnormal accumulation of alpha-synuclein is a defining feature of these disorders, implicated in the formation of Lewy bodies and the progression of neuronal dysfunction. Decades of study have illuminated facets of alpha-synuclein’s physiological roles and its pathogenic transformations, yet significant gaps persist in understanding its molecular behavior, aggregation dynamics, and the cascade of downstream effects triggered in neural tissues. Recent studies underscore the complexity of α-synuclein’s interactions with cellular pathways, including protein clearance mechanisms, immune regulation, and synaptic function. However, the translation of these molecular insights into clinical practice remains a topic of ongoing debate, particularly with respect to biomarker development and intervention strategies.This Research Topic aims to consolidate and advance current knowledge on alpha-synuclein by bringing together innovative research from basic, translational, and clinical domains. The principal objectives are to clarify the molecular underpinnings of alpha-synuclein pathology, evaluate its impact on neurodegeneration, neuroinflammation, and protein homeostasis, and to assess the validity and utility of alpha-synuclein as a diagnostic biomarker and therapeutic target. Key questions include understanding how alpha-synuclein modifications or aggregation contribute to disease progression, the efficacy of targeting alpha-synuclein in clinical trials, and identifying reliable measures for early diagnosis and monitoring response to therapy.Focusing on PD and related synucleinopathies, this Research Topic sets its boundaries to mechanistic, pathological, and translational aspects of alpha-synuclein biology, limiting its scope to peer-reviewed contributions grounded in experimental, clinical, or computational work. To gather further insights into this rapidly evolving field, we welcome articles addressing, but not limited to, the following themes:• Molecular mechanisms of alpha-synuclein misfolding, aggregation, and propagation• The role of alpha-synuclein in neuroinflammation and immune responses• Pathways involved in impaired protein clearance and proteostasis• The development and validation of alpha-synuclein-based biomarkers for diagnosis and disease monitoring• The clinical implications of targeting alpha-synuclein in neurodegenerative disease therapy• Advances in alpha-synuclein imaging and fluid biomarkers• Interactions between alpha-synuclein and other pathogenic proteins in synucleinopathiesTopic Editors Dr. Elpida Tsika, Dr. Francesca Capotosti, and Dr. Kirsten Scott are employees of AC Immune SA and are entitled to stock and/or stock options in the company. The remaining Topic Editors declare no commercial or financial relationships that could be construed as a potential conflict of interest. Topic editors: Maria Xilouri, Anne-Laure Mahul-Mellier, Kirsten Maurine Scott, Francesca Capotosti, Elpida Tsika, Julia Greenland Source: https://www.frontiersin.org/research-topics/79325/alpha-synuclein-in-parkinsons-disease-and-synucleinopathies-biology-pathogenic-mechanisms-and-clinical-relevance