The Involvement of the Peripheral Nervous System in Parkinson's Disease: Mechanistic and Diagnostic Implications

Parkinson’s Disease (PD) has traditionally been associated with the demise of central dopaminergic neurons. However, emerging evidence increasingly highlights the significance of the peripheral nervous system (PNS) in the disease’s pathogenesis and progression. Recent investigations, both clinical and preclinical, spotlight the manifestations of peripheral neural dysfunction such as autonomic failure, gastrointestinal issues, sensory disturbances, and neuropathies, which often predate or co-occur with the central motor and cognitive symptoms of PD. Peripheral tissue alterations–observed in muscles, skin, blood, kidneys, and autonomic nerves–shed light on early pathological changes, while systemic variations, including hepatic and metabolic dysfunctions, hint at extra-CNS contributions to neurodegeneration via neuroimmune and neurotoxic avenues. Peripheral dysfunction may not only reflect disease progression but also actively contribute to neurodegenerative processes through mechanisms such as alpha-synuclein propagation, immune activation, and peripheral neuroinflammation.This Research Topic seeks to explore the complex, bidirectional interactions between the central nervous system (CNS) and the numerous networks of the PNS, including those in autonomic, sensory, and enteric domains. Our goal is to solidify a systemic understanding of PD, centered around the pivotal yet underexplored role of peripheral nervous system dysfunction and peripheral-central neural interactions. By deepening our insights into these interactions, this Research Topic seeks to address key questions such as the role of alpha-synuclein propagation, immune activation, and peripheral neuroinflammation in neurodegeneration. Ultimately, it aims to bridge the existing CNS/PNS knowledge gaps to enrich understanding and inform innovative intervention strategies.The scope of this Research Topic is wide-ranging and inter-disciplinary, encompassing neurology, neuroimmunology, neurogastroenterology, neurophysiology, and translational neuroscience. To gather further insights into the involvement of the peripheral nervous system in Parkinson's disease pathogenesis and progression, we welcome submissions across a diverse range of manuscript types supported by the journal–including Original Research, Brief Research Reports, Perspectives, Protocols, Mini-Reviews, and more–exploring, but not limited to, the following themes:- Alpha-synuclein pathology in peripheral nerves: Mechanisms, clinical correlates, and its role in prion-like spread to the CNS.- Autonomic dysfunction in PD: Insights into cardiac, gastrointestinal, and urinary autonomic dyscontrol as markers and drivers of neurodegeneration.- Neuroimmune crosstalk: How peripheral immune activation or inflammation, as sensed or mediated by the PNS, influences CNS pathology.- Gut-brain-neural circuits: The impact of the enteric nervous system, gut-derived signals, and vagal pathways on PD risk, onset, and progression.- Peripheral biomarkers of neural dysfunction: Seeking early diagnostic and prognostic biomarkers in peripheral tissues, nerve fibers, or autonomic function tests.- Sensory and small fiber neuropathy: Clinical, pathological, and mechanistic insights into how peripheral neurodegeneration connects to PD symptomatology.- Neural pathways mediating systemic influences on the brain: How peripheral factors, through neural connections rather than purely metabolic or organ-based routes, modulate neuroinflammation, neurodegeneration, and synaptic dysfunction in PD.- Therapeutic implications: Modulation of peripheral neural circuits as a novel approach for symptom management and neuroprotection in PD.- Systems biology and multi-omics: Integrative approaches to uncover peripheral signatures of PD- Liver metabolism of neurotoxins and drugs: Implications for PD progression and treatment efficacyThis Research Topic aims to anchor the systemic view of PD firmly within the domain of neurology, emphasizing the underexplored yet critical roles of peripheral nervous system dysfunction and peripheral-central neural interplay.Articles accepted after peer review will be published and appear online as soon as approved for publication.Sign up now to participate in this exciting Research Topic. Topic editors: Juan F Reyes, Martin Ingelsson, VIncenzo Donadio Source: https://www.frontiersin.org/research-topics/75564/the-involvement-of-the-peripheral-nervous-system-in-parkinsons-disease-mechanistic-and-diagnostic-implications