Role of the Peripheral Nervous System in PD Pathology, Diagnosis, and Treatment

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.

Keywords: Parkinson’s disease; Schwann cell; dopaminergic neuron; graft; peripheral nervous.

FIGURE 1

Graphical illustration of PNS involving the pathology, diagnosis, treatment, therapeutic mechanism and safety of clinical application in PD.

FIGURE 2

Changes in SC after PNS injury and the performance of the nerve repair process. (A) Normal myelinated SC and basal lamina formation. (B) Post-injury, residual SCs upregulate repair-related signals into repaired SCs, which can align along the residual basal lamina to guide neuronal axon growth, while secreting cytokines and exosomes to promote neuronal survival and neurite growth. The repaired SCs also enhance phagocytosis to scavenge cell fragments, secreting inflammatory factors to regulate surrounding inflammation and recruiting macrophages into the injury to enhance cell fragment clearance. At this stage, the macrophage surface expresses a small amount of NgR. (C) After the repair is complete, the SC re-formed myelin sheath wraps around the axon and produces a basal lamina. The SC expresses MAG, which interacts with the macrophage surface NgR to induce the macrophage to migrate out of the nerve. At this stage, macrophage expression of NgR is significantly increased. SC, Schwann cell; PNS, peripheral nervous system; NgR, Nogo receptor; MAG, myelin-associated glycoprotein.