Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide, mainly affecting the elderly. The disease progresses gradually, with core motor presentations and a multitude of non-motor manifestations. There are two neuropathological hallmarks of PD, the dopaminergic neuronal loss and the alpha-synuclein-containing Lewy body inclusions in the substantia nigra. While the exact pathomechanisms of PD remain unclear, genetic investigations have revealed evidence of the involvement of mitochondrial function, alpha-synuclein (α-syn) aggregation, and the endo-lysosomal system, in disease pathogenesis. Due to the high energy demand of dopaminergic neurons, mitochondria are of special importance acting as the cellular powerhouse. Mitochondrial dynamic fusion and fission, and autophagy quality control keep the mitochondrial network in a healthy state. Should defects of the organelle occur, a variety of reactions would ensue at the cellular level, including disrupted mitochondrial respiratory network and perturbed calcium homeostasis, possibly resulting in cellular death. Meanwhile, α-syn is a presynaptic protein that helps regulate synaptic vesicle transportation and endocytosis. Its misfolding into oligomeric sheets and fibrillation is toxic to the mitochondria and neurons. Increased cellular oxidative stress leads to α-syn accumulation, causing mitochondrial dysfunction. The proteasome and endo-lysosomal systems function to regulate damage and unwanted waste management within the cell while facilitating the quality control of mitochondria and α-syn. This review will analyze the biological functions and interactions between mitochondria, α-syn, and the endo-lysosomal system in the pathogenesis of PD.

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Parkinson disease (PD) is the second most common neurodegenerative disease without known disease modification therapy to slow down disease progression. This disease has pathological features of Lewy bodies with α-synuclein aggregation being the major component and selective dopaminergic neuronal loss over the substantia nigra. Although the exact etiology is still unknown, mitochondrial dysfunction has been shown to be central in PD pathophysiology. Type 2 diabetes mellitus has recently been connected to PD, and anti-diabetic drugs, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), have been shown to possess neuroprotective effects in PD animal models. The GLP-1RA liraglutide is currently under a phase 2 clinical trial to measure its effect on motor and non-motor symptoms in PD patients. In this study, we used an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD to test the possible mechanism of the GLP-1RA liraglutide in the pathogenesis of PD. We show that the neurobehavioral and motor dysfunction caused by the mitochondrial complex I inhibitor, MPTP, can be partially reversed by liraglutide. The GLP-1RA can protect mice from apoptosis of substantia nigra neurons induced by MPTP. MPTP treatment led to imbalanced mitochondrial fusion and fission dynamics, altered mitochondrial morphology, impeded autophagy flux, increased α-synuclein accumulation, and elevated oxidative stress. Specifically, the normalizing of mitochondrial fusion-fission dynamic-related proteins and enhancement of autophagy flux after administration of liraglutide is associated with improving neuronal survival. This suggests that GLP-1RAs may provide potential beneficial effects for PD caused by mitochondrial dysfunction through improvement of mitochondrial morphology balance and enhancing damaged organelle degradation.

Parkinson's disease (PD) is a complex neurodegenerative disease with pathological hallmarks including progressive neuronal loss from the substantia nigra pars compacta and α-synuclein intraneuronal inclusions, known as Lewy bodies. Although the etiology of PD remains elusive, mitochondrial damage has been established to take center stage in the pathogenesis of PD. Mitochondria are critical to cellular energy production, metabolism, homeostasis, and stress responses; the association with PD emphasizes the importance of maintenance of mitochondrial network integrity. To accomplish the pleiotropic functions, mitochondria are dynamic not only within their own network but also in orchestrated coordination with other organelles in the cellular community. Through physical contact sites, signal transduction, and vesicle transport, mitochondria and intracellular organelles achieve the goals of calcium homeostasis, redox homeostasis, protein homeostasis, autophagy, and apoptosis. Herein, we review the finely tuned interactions between mitochondria and surrounding intracellular organelles, with focus on the nucleus, endoplasmic reticulum, Golgi apparatus, peroxisomes, and lysosomes. Participants that may contribute to the pathogenic mechanisms of PD will be highlighted in this review.

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 xc−/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.

Cardiovascular diseases are one of the leading causes of death and global health problems worldwide. Multiple factors are known to affect the cardiovascular system from lifestyles, genes, underlying comorbidities, and age. Requiring high workload, metabolism of the heart is largely dependent on continuous power supply via mitochondria through effective oxidative respiration. Mitochondria not only serve as cellular power plants, but are also involved in many critical cellular processes, including the generation of intracellular reactive oxygen species (ROS) and regulating cellular survival. To cope with environmental stress, mitochondrial function has been suggested to be essential during bioenergetics adaptation resulting in cardiac pathological remodeling. Thus, mitochondrial dysfunction has been advocated in various aspects of cardiovascular pathology including the response to ischemia/reperfusion (I/R) injury, hypertension (HTN), and cardiovascular complications related to type 2 diabetes mellitus (DM). Therefore, mitochondrial homeostasis through mitochondrial dynamics and quality control is pivotal in the maintenance of cardiac health. Impairment of the segregation of damaged components and degradation of unhealthy mitochondria through autophagic mechanisms may play a crucial role in the pathogenesis of various cardiac disorders. This article provides in-depth understanding of the current literature regarding mitochondrial remodeling and dynamics in cardiovascular diseases.

BACKGROUND An increasing number of studies have concluded that the number of adverse events in the upper airway caused by desflurane does not differ significantly from the number of adverse events caused by sevoflurane. The advantages of desflurane in ambulatory surgery should be reassessed. OBJECTIVES The aim of this study was to compare adverse respiratory events and recovery outcomes in patients undergoing desflurane or sevoflurane-based anaesthesia in ambulatory surgery. DESIGN A systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES A systematic search for eligible RCTs in PubMed, Medline, Cochrane Central Register of Controlled Trials, ScienceDirect and Embase published up to June 2019. ELIGIBILITY CRITERIA RCTs investigating the occurrence of adverse respiratory events, including airway irritation, stridor, coughing, respiratory distress and laryngospasm, emergence agitation, postoperative nausea and vomiting (PONV), time to eye opening and time to discharge from the operation room after desflurane or sevoflurane-based anaesthesia. RESULTS Thirteen trials were included and analysed. A total of 634 patients were included in the desflurane group, and 633 patients in the sevoflurane group. The occurrence of respiratory complications was significantly higher with desflurane-based anaesthesia than with sevoflurane-based anaesthesia (Total n = 673, 20.0 vs. 12.8%, relative risk (RR) 1.59 (95% CI 1.15 to 2.20)) with low heterogeneity ( I 2 = 20%). There was no difference in the occurrence of emergence agitation (Total n = 626, 29.1 vs. 27.2%, RR 1.05 (95% CI 0.84 to 1.30)) or the incidence of PONV between the desflurane and sevoflurane groups (Total n = 989, 19.0 vs. 21.0%, RR 0.95 (95% CI 0.71 to 1.26)). Time to eye opening was significantly faster with desflurane than that with sevoflurane (Total n = 1072, mean difference = −3.32 min (95% CI −4.02 to −2.61)) with a substantial heterogeneity ( I 2 = 72.6%). There was no significant difference in the time to discharge from the operation room between the two groups (Total n = 1056, mean difference = −0.45 min (95% CI −5.89 to 4.99)). CONCLUSION Despite recent reports that there is no significant difference in adverse respiratory events between desflurane and sevoflurane, a pooled analysis revealed that desflurane resulted in a higher rate than sevoflurane. Therefore, the consequences of desflurane should not be neglected and its airway irritant properties should be taken into account. TRIAL REGISTRATION PROSPERO (CRD42019147939).

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.