Hovgaardmccoy1496

G regulation by PGC-1α plays an essential role in rotenone-induced neurotoxicity in PC12 cells. EXOG represents a protective effect strategy in PC12 cells exposed to rotenone.FHL1-related myopathies are rare X-linked dominant myopathies. Though clinically classified into several subgroups, spinal and scapuloperoneal muscle involvement are common to all. In this study, we identified c.449G > A, p.C150Y mutation by clinical exome sequencing in two patients from same family (son and mother) of Indian origin who presented with multiple contractures. Muscle biopsy showed numerous intracytoplasmic aggregates intensely stained on HE and MGT. The strong reactions to M-NBT revealed aggregates to be reducing bodies and positively labeled to anti-FHL1 antibody. Ultrastructurally, Z-band streaming and granular and granulofilamentous material were seen. Further, the translational evidence of mutant peptide was confirmed using mass spectrometric analysis. To establish p.C150Y as the cause for protein aggregation, in vivo studies were carried out using transgenic Drosophila model which highlighted Z-band abnormalities and protein aggregates in indirect flight muscles with compromised physiological function. Thus, recapitulating the X-linked human disease phenotype. Additionally, the molecular dynamics simulation analysis unraveled the drastic change in α-helix of LIM2, the region immediately next to site of C150Y mutation that could be the plausible cause for protein aggregation. DMOG To the best of our knowledge, this is the first study of p.C150Y mutation in FHL1 identified in Indian patients with in vivo and in silico analysis to establish the cause for protein aggregation in muscle.Neurological diseases share common neuroinflammatory and oxidative stress pathways. Both phenotypic and molecular changes in microglia, astrocytes, and neurons contribute to the progression of disease and present potential targets for disease modification. Src family kinases (SFKs) are present in both neurons and glial cells and are upregulated following neurological insults in both human and animal models. In neurons, SFKs interact with post-synaptic protein domains to mediate hyperexcitability and neurotoxicity. SFKs are upstream of signaling cascades that lead to the modulation of neurotransmitter receptors and the transcription of pro-inflammatory cytokines as well as producers of free radicals through the activation of glia. Inducible nitric oxide synthase (iNOS/NOS-II) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), the major mediators of reactive nitrogen/oxygen species (RNS/ROS) production in the brain, are also upregulated along with the pro-inflammatory cytokines following neurological insult and contribute to disease progression. Persistent neuronal hyperexcitability, RNS/ROS, and cytokines can exacerbate neurodegeneration, a common pathognomonic feature of the most prevalent neurological disorders such as Alzheimer's disease, Parkinson's disease, and epilepsy. Using a wide variety of preclinical disease models, inhibitors of the SFK-iNOS-NOX2 signaling axis have been tested to cure or modify disease progression. In this review, we discuss the SFK-iNOS-NOX2 signaling pathway and their inhibitors as potential CNS targets for major neurological diseases.Brain insulin signaling contributes to memory function and might be a viable target in the prevention and treatment of memory impairments including Alzheimer's disease. This short narrative review explores the potential of central nervous system (CNS) insulin administration via the intranasal pathway to improve memory performance in health and disease, with a focus on the most recent results. Proof-of-concept studies and (pilot) clinical trials in individuals with mild cognitive impairment or Alzheimer's disease indicate that acute and prolonged intranasal insulin administration enhances memory performance, and suggest that brain insulin resistance is a pathophysiological factor in Alzheimer's disease with or without concomitant metabolic dysfunction. Intranasally administered insulin is assumed to trigger improvements in synaptic plasticity and regional glucose uptake as well as alleviations of Alzheimer's disease neuropathology; additional contributions of changes in hypothalamus-pituitary-adrenocortical axis activity and sleep-related mechanisms are discussed. While intranasal insulin delivery has been conclusively demonstrated to be effective and safe, the recent outcomes of large-scale clinical studies underline the need for further investigations, which might also yield new insights into sex differences in the response to intranasal insulin and contribute to the optimization of delivery devices to grasp the full potential of intranasal insulin for Alzheimer's disease.

Asprosin, a recently discovered adipokine, stimulates the release of hepatic glucose. The purpose of the current research was to determine the relation between serum asprosin and obstructive sleep apnea syndrome (OSAS).

The current investigation enrolled 152 patients with OSAS and 97 control subjects. Serum asprosin concentrations were measured and analyzed.

Higher serum asprosin concentrations were found in patients withOSAS than in the controls. Logistic regression analysis demonstrated that serum asprosin concentrations were associated with an increased risk of OSAS. Patients with severe OSAS had significantly increased asprosin compared to mild and moderate groups. The group with moderate OSAS showed higher serum asprosinlevels than the group withmild OSAS. Pearson correlation analysis demonstrated a positive relation between serum asprosin and disease severity. Simple linear regression analyses showed a significant correlation between serum asprosin with body mass index (BMI), fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), and apnea-hypopnea index (AHI), and negatively correlated with high-density lipoprotein cholesterol (HDL-C). Multiple linear regression analysis revealed a significant correlation between serum asprosin with BMI, FPG, HOMA-IR, TG, AHI, and HDL-C.

There is a significant correlation between serum asprosin with the presence and severity of OSAS.

There is a significant correlation between serum asprosin with the presence and severity of OSAS.