Abstract

Studies on Parkinson disease (PD) have mostly focused on the central nervous system—specifically, on the loss of mesencephalic dopaminergic neurons and associated motor dysfunction. However, the peripheral nervous system (PNS) is gaining prominence in PD research, with increasing clinical attention being paid to non-motor symptoms. Researchers found abnormal deposition of α-synuclein and neuroinflammation in the PNS. Attempts have been made to use these pathological changes during the clinical diagnosis of PD. Animal studies demonstrated that combined transplantation of autologous peripheral nerves and cells with tyrosine hydroxylase activity can reduce dopaminergic neuronal damage, and similar effects were observed in some clinical trials. In this review, we will systematically explain PNS performance in PD pathology and its clinical diagnostic research, describe PNS experimental results [especially Schwann cell (SC) transplantation in the treatment of PD animal models] and the results of clinical trials, and discuss future directions. The mechanism by which SCs produce such a therapeutic effect and the safety of transplantation therapy are briefly described.

Highlights

  • Parkinson disease (PD) is a typical neurodegenerative disorder of the nervous system

  • The 6-stage theory proposed by Braak to explain the pathology and clinical development of PD postulates that neurodegeneration begins in the peripheral nervous system (PNS), with progressive involvement of the central nervous system (CNS) from caudal to rostral brain areas and corresponding clinical manifestations (Braak et al, 2003; Braak and Del Tredici, 2017)

  • The PNS is relevant to the diagnosis and treatment of PD, but its clinical application has not been fully exploited

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Summary

Introduction

Parkinson disease (PD) is a typical neurodegenerative disorder of the nervous system. A recent clinical study reported that phosphorylated α-synuclein deposits were present in SCs of the sural nerve in PD patients but almost absent in axons (Zhang et al, 2019). Axonal degeneration of peripheral nerves and activation of SCs with secretion of multiple inflammatory factors are observed in PD patients, but these lesions are not necessarily associated with sensory abnormalities in patients (Zhang et al, 2020).

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