Peripheral nervous system involvement in Parkinson's disease: Peripheral neuropathy, neuromuscular junction...

Area of Science:

• Neuroscience
• Neurology
• Pathology

Background:

• Parkinson's disease (PD) is traditionally viewed as a central nervous system disorder.
• Emerging evidence highlights the significant role of the peripheral nervous system (PNS) in PD initiation, progression, and symptom heterogeneity.
• Peripheral pathways, including sensory, autonomic, and motor nerves, exhibit abnormalities in PD.

Purpose of the Study:

• To synthesize the current understanding of PNS involvement in Parkinson's disease.
• To elucidate the relationship between peripheral pathology and central neurodegeneration using a framework of causal, parallel, and secondary processes.
• To review diagnostic advancements and therapeutic strategies targeting peripheral manifestations of PD.

Main Methods:

• Review of clinical and pathological evidence for PNS involvement in PD.
• Analysis of mechanisms maintaining peripheral nerve function (e.g., neurotrophic factors, NMJ integrity).
• Integration of converging pathological mechanisms (e.g., alpha-synuclein, immune activation, mitochondrial dysfunction).

Main Results:

• Peripheral neuropathy and PNS abnormalities are evident in PD, manifesting as motor, autonomic, and sensory symptoms.
• Mechanisms like alpha-synuclein pathology, immune responses, and mitochondrial dysfunction disrupt peripheral nerve homeostasis.
• Advances in diagnostics include nerve conduction studies, EMG, and peripheral alpha-synuclein detection.

Conclusions:

• The PNS plays a critical, clinically relevant role in Parkinson's disease.
• Understanding peripheral mechanisms is essential for improving early PD detection and guiding future therapeutic development.
• Integrating peripheral approaches into PD research and treatment is vital for comprehensive patient care.