Background The coronavirus disease 2019 (COVID-19) pandemic is adversely affecting sleep quality and mental health, especially in individuals with chronic disease such as Parkinson's disease (PD). Methods We conducted a quantitative study, which included 119 Chinese PD patients who had been treated in an outpatient neurology clinic in Wuhan and 169 age- and sex-matched healthy controls. The questionnaire survey focused on the impact of the COVID-19 pandemic on sleep, mental status, symptoms, and daily life and medical treatment of PD patients. Results Compared to healthy controls, PD patients had significantly higher scores in both the Pittsburgh Sleep Quality Index (PSQI) (8.13 vs 5.36, p < 0.001) and the Hospital Anxiety and Depression Scale (HADS) -Depression (4.89 vs 3.82, p = 0.022), as well as a higher prevalence of sleep disturbances with PSQI > 5 points (68.9% vs 44.4%, p < 0.001). Sleep disturbance was identified in 68.9% of PD patients. A logistic regression analysis showed that sleep disturbance of PD patients was independently associated with exacerbation of PD symptoms (OR = 3.616, 95%CI= (1.479, 8.844), p = 0.005) and anxiety (OR = 1.379, 95%CI= (1.157, 1.642), p < 0.001). Compared to male PD patients, female ones had higher PSQI scores (9.28 ± 4.41 vs 7.03 ± 4.01, p = 0.009) and anxiety (32.8% vs 0.1%, p = 0.002) and depression prevalence (34.5% vs 11.5%, p = 0.003). Conclusion The findings of the present study emphasize the importance of mental and sleep health interventions in PD patients during the COVID-19 pandemic. Additional attention should be paid to the difficulty encountered by PD patients in seeking medical treatment.

Increasing evidence suggests that microglial activation is strongly linked to the initiation and progression of Parkinson’s disease (PD). Cell-to-cell propagation of α-synuclein (α-syn) pathology is a highlighted feature of PD, and the focus of such research has been primarily on neurons. However, recent studies as well as the data contained herein suggest that microglia, the primary phagocytes in the brain, play a direct role in the spread of α-syn pathology. Recent data revealed that plasma exosomes derived from PD patients (PD-EXO) carry pathological α-syn and target microglia preferentially. Hence, PD-EXO is likely a key tool for investigating the role of microglia in α-syn transmission. We showed that intrastriatal injection of PD-EXO resulted in the propagation of exosomal α-syn from microglia to neurons following microglia activation. Toll-like receptor 2 (TLR2) in microglia was activated by exosomal α-syn and acted as a crucial mediator of PD-EXO-induced microglial activation. Additionally, partial microglia depletion resulted in a significant decrease of exogenous α-syn in the substantia nigra (SN). Furthermore, exosomal α-syn internalization was initiated by binding to TLR2 of microglia. Excessive α-syn phagocytosis may induce the inflammatory responses of microglia and provide the seed for microglia-to-neuron transmission. Consistently, TLR2 silencing in microglia mitigated α-syn pathology in vivo. Overall, the present data support the idea that the interaction of exosomal α-syn and microglial TLR2 contribute to excessive α-syn phagocytosis and microglial activation, which lead to the further propagation and spread of α-syn pathology, thereby highlighting the pivotal roles of reactive microglia in α-syn transmission.

According to emerging studies, the excessive activation of microglia and the subsequent release of pro-inflammatory cytokines play important roles in the pathogenesis and progression of Parkinson’s disease (PD). However, the exact mechanisms governing chronic neuroinflammation remain elusive. Findings demonstrate an elevated level of NLRP3 inflammasome in activated microglia in the substantia nigra of PD patients. Activated NLRP3 inflammasome aggravates the pathology and accelerates the progression of neurodegenerative diseases. Abnormal protein aggregation of α-synuclein (α-syn), a pathologically relevant protein of PD, were reported to activate the NLRP3 inflammasome of microglia through interaction with toll-like receptors (TLRs). This eventually releases pro-inflammatory cytokines through the translocation of nuclear factor kappa-B (NF-κB) and causes an impairment of mitochondria, thus damaging the dopaminergic neurons. Currently, therapeutic drugs for PD are primarily aimed at providing relief from its clinical symptoms, and there are no well-established strategies to halt or reverse this disease. In this review, we aimed to update existing knowledge on the role of the α-syn/TLRs/NF-κB/NLRP3 inflammasome axis and microglial activation in PD. In addition, this review summarizes recent progress on the α-syn/TLRs/NF-κB/NLRP3 inflammasome axis of microglia as a potential target for PD treatment by inhibiting microglial activation.