Parkinson disease (PD) is the second-most common neurodegenerative disease. The characteristic pathology of progressive dopaminergic neuronal loss in people with PD is associated with iron accumulation and is suggested to be driven in part by the novel cell death pathway, ferroptosis. A unique modality of cell death, ferroptosis is mediated by iron-dependent phospholipid peroxidation. The mechanisms of ferroptosis inhibitors enhance antioxidative capacity to counter the oxidative stress from lipid peroxidation, such as through the system x_c⁻/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis and the coenzyme Q10 (CoQ10)/FSP1 pathway. Another means to reduce ferroptosis is with iron chelators. To date, there is no disease-modifying therapy to cure or slow PD progression, and a recent topic of research seeks to intervene with the development of PD via regulation of ferroptosis. In this review, we provide a discussion of different cell death pathways, the molecular mechanisms of ferroptosis, the role of ferroptosis in blood–brain barrier damage, updates on PD studies in ferroptosis, and the latest progress of pharmacological agents targeting ferroptosis for the intervention of PD in clinical trials.

Excessive reactive oxygen species (ROS) contribute to damage of retinal cells and the development of retinal diseases including age‐related macular degeneration (AMD). ROS result in increased metabolites of lipoxygenases (LOXs), which react with ROS to induce lipid peroxidation and may lead to ferroptosis. In this study, the effect of 5‐LOX inhibition on alleviating ROS‐induced cell death was evaluated using sodium iodate (NaIO₃) in the retinal pigment epithelium (RPE) cell line ARPE‐19 and a mouse model investigating oxidative stress in AMD. We demonstrated that NaIO₃ induced cell death in the RPE cells through mechanisms including ferroptosis. Inhibition of 5‐LOX with specific inhibitor, Zileuton, or siRNA knockdown of ALXO5 mitigated NaIO₃‐induced lipid peroxidation, mitochondrial damage, DNA impairment, and cell death in ARPE‐19 cells. Additionally, in the mouse model, pretreatment with Zileuton reduced the NaIO₃‐induced lipid peroxidation of RPE cells, cell death in the photoreceptor layer of the retina, inflammatory responses, and degeneration of both the neuroretina and RPE monolayer cells. Our results suggest that 5‐LOX plays a crucial role in ROS‐induced cell death in the RPE and that regulating 5‐LOX activity could be a useful approach to control ROS and ferroptosis‐induced damage, which promote degeneration in retinal diseases.

Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease affecting more than 1% of the population over 65 years old. The etiology of the disease is unknown and there are only symptomatic managements available with no known disease-modifying treatment. Aging, genes, and environmental factors contribute to PD development and key players involved in the pathophysiology of the disease include oxidative stress, mitochondrial dysfunction, autophagic–lysosomal imbalance, and neuroinflammation. Recent epidemiology studies have shown that type-2 diabetes (T2DM) not only increased the risk for PD, but also is associated with PD clinical severity. A higher rate of insulin resistance has been reported in PD patients and is suggested to be a pathologic driver in this disease. Oral diabetic drugs including sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors have been shown to provide neuroprotective effects in both PD patients and experimental models; additionally, antidiabetic drugs have been demonstrated to lower incidence rates of PD in DM patients. Among these, the most recently developed drugs, SGLT2 inhibitors may provide neuroprotective effects through improving mitochondrial function and antioxidative effects. In this article, we will discuss the involvement of mitochondrial-related oxidative stress in the development of PD and potential benefits provided by antidiabetic agents especially focusing on sglt2 inhibitors.

Purpose: To evaluate the impact of macular serous retinal detachment (SRD) and its relationship to treatment outcome after primary intravitreal bevacizumab (IVB) injection in patients with branch retinal vein occlusion (BRVO) and macular edema (ME). Methods: Seventy-three patients with ME secondary to BRVO who received primary IVB (2.5 mg/0.1 mL) were included in this study. The specific ME patterns were investigated using optical coherence tomography (OCT) examination. Visual acuity (VA), central macular thickness (CMT), and macular volume at baseline; at 1, 3, and 6 months; and at final visit after primary IVB were retrospectively analyzed and compared between patients with and without SRD. Results: SRD was found in 25 patients (34.2%). The baseline CMT was significantly thicker in patients with SRD than in those without it (648.4±200.5 μm vs. 440.3±119.6 μm, P <0.001). Six months after primary IVB injection, a greater reduction in CMT change from baseline was observed in the SRD group (412.5±227.2 μm) than in the group without SRD (118.5±175.2 μm) ( P <0.001). The improvement of logarithm of the minimum angle of resolution VA was also greater in the SRD group than in the group without SRD (−0.64±0.52 and −0.28±0.62 respectively, P =0.015). Logistic regression analysis showed that the presence of SRD was an independent factor for visual improvement in BRVO ( P =0.027). Conclusion: Patients with SRD had greater functional and morphological improvements at 6 months after primary IVB therapy. The results of this study suggest that the presence of SRD observed on OCT may be an indicator of favorable clinical response after IVB injections and that in BRVO patients with SRD, bevacizumab may be a good alternative for treatment.