Anatomy of Parkinson’s Disease and Synucleinopathies: From Neuronal Circuits to Peripheral Organs

Parkinson’s Disease (PD) stands as the second most prevalent neurodegenerative disorder. Classically described as a disease affecting dopaminergic neurons and the meso-striatal dopaminergic pathway, recent findings have connected PD to the degeneration of multiple neuronal circuits, extending to the peripheral nervous system and visceral organs. This broader perspective challenges the efficacy of dopaminergic therapies, particularly for the non-motor symptoms of PD, as their neuroanatomical and neurophysiological basis remains elusive. The involvement of visceral organs, where alpha-synuclein (a-syn) pathology has been reported in both functional cells and autonomic nervous fibers, adds another layer of complexity. Notably, for certain PD subtypes, peripheral manifestations may emerge prior to central nervous system involvement. This peripheral aspect is significant as it renders tissue easily obtainable for bio-sample collection. Other synucleinopathies, including multiple system atrophy (MSA), Lewy Bodies Dementia (LBD) and pure autonomic failure, are also poorly understood in their anatomical background, leading to a frequent clinical misdiagnosis at the early stages of the disease.

The primary objective of this Research Topic is to elucidate the roles of different neuronal circuits and visceral organs in the pathology and pathophysiology of Parkinson’s disease and other synucleinopathies. By delineating the precise anatomical distribution of alpha-synuclein pathology, we aim to better understanding the specific clinical symptoms of PD and other synucleinopathies, laying the groundwork for innovative therapeutic interventions. Concurrently, by examining the involvement of visceral organs and peripheral nervous system, we aim to identify novel molecular biomarker sources or enhance the validation of existing ones. Finally, giving the intriguing hypothesis of a body-first versus brain-first PD onset pattern, we also aim to elucidate their differential neuroanatomical distributions and neuropathological progressions, encompassing the possible role of microbiome, as well as the identification of radiological and molecular biomarkers capable of distinguishing between these different pathological and clinical subtypes.

For this Research Topic, we invite Review and Original Research articles that shed light on the anatomical distribution of neurodegeneration and alpha synuclein pathology both in the central nervous system and in visceral organs. Especially encouraged are scholarly contributions that correlate anatomical observations with possible novel therapeutic approaches, or with the development of new radiological, pathological and molecular biomarkers.