Search results for "mito"
showing 10 items of 2513 documents
Current disease modifying approaches to treat Parkinson's disease
2015
Parkinson's disease (PD is a progressive neurological disorder characterized by the degeneration and death of midbrain dopamine and non-dopamine neurons in the brain leading to motor dysfunctions and other symptoms, which seriously influence the quality of life of PD patients. The drug L-dopa can alleviate the motor symptoms in PD, but so far there are no rational therapies targeting the underlying neurodegenerative processes. Despite intensive research, the molecular mechanisms causing neuronal loss are not fully understood which has hampered the development of new drugs and disease-modifying therapies. Neurotrophic factors are by virtue of their survival promoting activities attract candi…
Palmitic Acid: Physiological Role, Metabolism and Nutritional Implications
2017
Palmitic acid (PA) has been for long time negatively depicted for its putative detrimental health effects, shadowing its multiple crucial physiological activities. PA is the most common saturated fatty acid accounting for 20–30% of total fatty acids in the human body and can be provided in the diet or synthesized endogenously via de novo lipogenesis (DNL). PA tissue content seems to be controlled around a well-defined concentration, and changes in its intake do not influence significantly its tissue concentration because the exogenous source is counterbalanced by PA endogenous biosynthesis. Particular physiopathological conditions and nutritional factors may strongly induce DNL, resulting i…
The Mitochondria-Targeted Antioxidant MitoQ Modulates Mitochondrial Function and Endoplasmic Reticulum Stress in Pancreatic β Cells Exposed to Hyperg…
2019
Background/aims Mitochondria-targeted antioxidants such as mitoquinone (MitoQ) have demonstrated protective effects against oxidative damage in several diseases. The increase in reactive oxygen species (ROS) production during glucose metabolism in β cells can be exacerbated under hyperglycaemic conditions such as type 2 diabetes (T2D), thus contributing to β cell function impairment. In the present work, we aimed to evaluate the effect of MitoQ on insulin secretion, oxidative stress, endoplasmic reticulum (ER) stress and nuclear factor kappa B (NFκB) signalling in a pancreatic β cell line under normoglycaemic (NG, 11.1 mM glucose), hyperglycaemic (HG, 25 mM glucose) and lipidic (palmitic ac…
Obesogenic Diets Cause Alterations on Proteins and Theirs Post-Translational Modifications in Mouse Brains
2021
Obesity constitutes a major global health threat and is associated with a variety of diseases ranging from metabolic and cardiovascular disease, cancer to neurodegeneration. The hallmarks of neurodegeneration include oxidative stress, proteasome impairment, mitochondrial dysfunction and accumulation of abnormal protein aggregates as well as metabolic alterations. As an example, in post-mortem brain of patients with Alzheimer’s disease (AD), several studies have reported reduction of insulin, insulin-like growth factor 1 and insulin receptor and an increase in tau protein and glycogen-synthase kinase-3β compared to healthy controls suggesting an impairment of metabolism in the AD patient’s …
Olesoxime improves cerebral mitochondrial dysfunction and enhances Aβ levels in preclinical models of Alzheimer's disease.
2019
Abstract Background Approved drugs for Alzheimer's disease (AD) only have a symptomatic effects and do not intervene causally in the course of the disease. Olesoxime (TRO19622) has been tested in AD disease models characterized by improved amyloid precursor protein processing (AβPP) and mitochondrial dysfunction. Methods Three months old Thy-1-AβPPSL (tg) and wild type mice (wt) received TRO19622 (100 mg/kg b.w.) in supplemented food pellets for 15 weeks (tg TRO19622). Mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) levels were determined in dissociated brain cells (DBC). Respiration was analyzed in mitochondria isolated from brain tissue. Citrate synthase (CS) activ…
Atorvastatin but not pravastatin impairs mitochondrial function in human pancreatic islets and rat β-cells. Direct effect of oxidative stress
2017
AbstractStatins are a class of drugs widely prescribed as frontline therapy for lowering plasma LDL-cholesterol in cardiovascular risk prevention. Several clinical reports have recently suggested an increased risk of type 2 diabetes associated with chronic use of these drugs. The pathophysiology of this effect remains to be fully elucidated but impaired β-cell function constitutes a potential mechanism. The aim of this study was to explore the effect of a chronic treatment with lipophilic and hydrophilic statins on β-cell function, using human pancreatic islets and rat insulin-secreting INS-1 cells; we particularly focused on the role of mitochondria and oxidative stress. The present study …
Can mild cognitive impairment be stabilized by showering brain mitochondria with laser photons?
2019
There is now substantial evidence that cerebral blood flow (CBF) declines with age. From age 20 to 60, CBF is estimated to dip about 16% and continues to drop at a rate of 0.4%/year. This CBF dip will slowly reduce oxygen/glucose delivery to brain thus lowering ATP energy production needed by brain cells to perform normal activities. Reduced ATP production from mitochondrial loss or damage in the wear-and-tear of aging worsens when vascular risk factors (VRF) to Alzheimer's disease develop that can accelerate both age-decline CBF and mitochondrial deficiency to a level where mild cognitive impairment (MCI) develops. To date, no pharmacological or any other treatment has been successful in r…
Mitochondrial DNA Haplogroup JT is Related to Impaired Glycaemic Control and Renal Function in Type 2 Diabetic Patients
2018
The association between mitochondrial DNA (mtDNA) haplogroup and risk of type 2 diabetes (T2D) is undetermined and controversial. This study aims to evaluate the impact of the main mtDNA haplogroups on glycaemic control and renal function in a Spanish population of 303 T2D patients and 153 healthy controls. Anthropometrical and metabolic parameters were assessed and mtDNA haplogroup was determined in each individual. Distribution of the different haplogroups was similar in diabetic and healthy populations and, as expected, T2D patients showed poorer glycaemic control and renal function than controls. T2D patients belonging to the JT haplogroup (polymorphism m.4216T>
Branched-Chain Amino Acid Levels Are Related with Surrogates of Disturbed Lipid Metabolism among Older Men.
2016
Aims/hypothesis: Existing studies suggest that decreased branched-chain amino acid (BCAA) catabolism and thus elevated levels in blood are associated with metabolic disturbances. Based on such information, we have developed a hypothesis how BCAA degradation mechanistically connects to tricarboxylic acid cycle, intramyocellular lipid storage, and oxidation, thus allowing more efficient mitochondrial energy production from lipids as well as providing better metabolic health. We analyzed whether data from aged Finnish men are in line with our mechanistic hypothesis linking BCAA catabolism and metabolic disturbances. Methods: Older Finnish men enriched with individuals having been athletes in y…
Antiepileptogenic Effect of Subchronic Palmitoylethanolamide Treatment in a Mouse Model of Acute Epilepsy
2018
Research on the antiepileptic effects of (endo-)cannabinoids has remarkably progressed in the years following the discovery of fundamental role of the endocannabinoid (eCB) system in controlling neural excitability. Moreover, an increasing number of well-documented cases of epilepsy patients exhibiting multi-drug resistance report beneficial effects of cannabis use. Pre-clinical and clinical research has increasingly focused on the antiepileptic effectiveness of exogenous administration of cannabinoids and/or pharmacologically induced increase of eCBs such as anandamide (also known as arachidonoylethanolamide [AEA]). Concomitant research has uncovered the contribution of neuroinflammatory p…