White matter lesions contribute to motor and non-motor disorders in Parkinson's disease: a critical review.

Parkinson's disease (PD) is a prevalent neurodegenerative disease, characterized by movement disorders and non-motor symptoms like cognitive impairment and depression. Degeneration of dopaminergic neurons in the substantia nigra and Lewy bodies have long been considered as main neuropathological changes. However, recent magnetic resonance imaging (MRI) studies have shown that white matter lesions (WMLs) were present in PD patients. WMLs are characterized by loss or impairment of myelin sheath in central nerve fibers, which are closely correlated with motor and cognitive dysfunction in PD. WMLs alterations precede nigrostriatal neuronal losses and can independently affect the clinical severity or characteristics of motor coordination in PD patients. Currently, the exact mechanism of WMLs involvement in the occurrence and development of PD remains unclear. It is speculated that WMLs may participate in the pathogenesis of PD by disrupting important connections in brain or promoting axonal degeneration. In this review, we will discuss the pathological changes and mechanisms of WMLs, elaborate the impact of WMLs on the progression of PD, clarify the importance of WMLs in PD pathogenesis, and thus provide novel targets for PD treatments.