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Background: Emerging evidence indicates that the apolipoprotein E (APOE) ε4 exacerbates α‐synuclein pathology. Objective: To determine whether APOE ε4 contributes to motor progression in early Parkinson's disease (PD). Methods: Longitudinal data were obtained from 384 patients with PD divided into APOE ε4 carriers (n = 85) and noncarriers (n = 299) in the Parkinson's Progression Marker Initiative. Participants underwent yearly motor assessments over a mean follow‐up period of 78.9 months. Repeated measures and linear mixed models were used to test the effects of APOE ε4. Results: The motor progression was significantly more rapid in patients with PD carrying APOE ε4 than in noncarriers (β = 0.283, P = 0.026, 95% confidence interval: 0.033–0.532). Through subgroup analysis, we found that the effect of APOE ε4 was significant only in patients with high amyloid β burden (β = 0.761, P < 0.001, 95% confidence interval: 0.0356–1.167). Conclusions: APOE ε4 may be associated with rapid motor progression in PD. © 2021 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Targeted sequencing of Parkinson's disease loci genes s SYT11, FGF20 and other associations. Taken together, our results indicated that the 10 variants in I SYT11 i , I FGF20 i , I GCH1 i genes may not be causative variants for PD in eastern China. One nonsynonymous variant (position: 55312562; c.C552T, p.R186C) in the I GCH1 i gene was found in eight PD patients and four healthy controls (Table 1). [Extracted from the article]

Ferroptosis, a novel form of regulated cell death, is caused by accumulation of lipid peroxides and excessive iron deposition. This process has been linked to the death of dopaminergic neurons in substantia nigra compacta (SNc) of Parkinson's disease (PD) patients. Quercetin (QCT), a natural flavonoid, has multiple pharmacological activities. However, it has not been established whether QCT can protect against dopaminergic neuron death by inhibiting ferroptosis. In this study, we investigated the potential antiferroptotic effects of QCT in cellular models established using specific ferroptosis inducers (Erastin and RSL-3) and MPP + . The effects were also explored using MPTP-induced PD mouse models. The cell counting kit-8 (CCK-8) assay was performed to assess cell viability. Variations in mitochondrial morphology were evaluated by transmission electron microscopy (TEM) while the mitochondrial membrane potential, mass, and ROS were measured by fluorescent probes. Lipid peroxidation levels were assayed through measurement of lipid ROS, MDA, GSH, and SOD levels. The effects of QCT on MPTP-induced behavioral disorders were examined by rotarod and open field tests. In vitro and in vivo , QCT significantly inhibited ferroptosis by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) protein. Additionally, QCT ameliorated motor behavioral impairments and protected against the loss of dopaminergic neurons in MPTP-induced PD models. Interestingly, Nrf2 knockdown alleviated the protective effects of QCT against ferroptosis. In conclusion, these results demonstrate that ferroptosis is involved in MPP + /MPTP-induced PD, and QCT inhibits ferroptosis by activating the Nrf2 protein. Therefore, QCT is a potential agent for preventing the loss of dopaminergic neurons by targeting ferroptosis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Zhi-Hao Lin et al.)