scholarly journals Targeting Mitochondria as Therapeutic Strategy for Metabolic Disorders

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Daniela Sorriento ◽  
Antonietta Valeria Pascale ◽  
Rosa Finelli ◽  
Anna Lisa Carillo ◽  
Roberto Annunziata ◽  
...  

Mitochondria are critical regulator of cell metabolism; thus, mitochondrial dysfunction is associated with many metabolic disorders. Defects in oxidative phosphorylation, ROS production, or mtDNA mutations are the main causes of mitochondrial dysfunction in many pathological conditions such as IR/diabetes, metabolic syndrome, cardiovascular diseases, and cancer. Thus, targeting mitochondria has been proposed as therapeutic approach for these conditions, leading to the development of small molecules to be tested in the clinical scenario. Here we discuss therapeutic interventions to treat mitochondrial dysfunction associated with two major metabolic disorders, metabolic syndrome, and cancer. Finally, novel mechanisms of regulation of mitochondrial function are discussed, which open new scenarios for mitochondria targeting.

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1195 ◽  
Author(s):  
Rahat Ullah ◽  
Mehtab Khan ◽  
Shahid Ali Shah ◽  
Kamran Saeed ◽  
Myeong Ok Kim

All over the world, metabolic syndrome constitutes severe health problems. Multiple factors have been reported in the pathogenesis of metabolic syndrome. Metabolic disorders result in reactive oxygen species (ROS) induced oxidative stress, playing a vital role in the development and pathogenesis of major health issues, including neurological disorders Alzheimer’s disease (AD) Parkinson’s disease (PD). Considerable increasing evidence indicates the substantial contribution of ROS-induced oxidative stress in neurodegenerative diseases. An imbalanced metabolism results in a defective antioxidant defense system, free radicals causing inflammation, cellular apoptosis, and tissue damage. Due to the annual increase in financial and social burdens, in addition to the adverse effects associated with available synthetic agents, treatment diversion from synthetic to natural approaches has occurred. Antioxidants are now being considered as convincing therapeutic agents against various neurodegenerative disorders. Therefore, medicinal herbs and fruits currently receive substantially more attention as commercial sources of antioxidants. In this review, we argue that ROS-targeted therapeutic interventions with naturally occurring antioxidant flavonoid, anthocyanin, and anthocyanin-loaded nanoparticles might be the ultimate treatment against devastating illnesses. Furthermore, we elucidate the hidden potential of the neuroprotective role of anthocyanins and anthocyanin-loaded nanoparticles in AD and PD neuropathies, which lack sufficient attention compared with other polyphenols, despite their strong antioxidant potential. Moreover, we address the need for future research studies of native anthocyanins and nano-based-anthocyanins, which will be helpful in developing anthocyanin treatments as therapeutic mitochondrial antioxidant drug-like regimens to delay or prevent the progression of neurodegenerative diseases, such as AD and PD.


2015 ◽  
Vol 6 (3) ◽  
pp. 33-37
Author(s):  
E. M Surkichin ◽  
I. P Shuvaev ◽  
E. U Asymbekova ◽  
S. T Matskeplishvili

Metabolic syndrome represents a combination of different major risk factors of cardiovascular diseases and is mainly related to impaired insulin sensitivity in biological tissues. Common understanding of pathogenesis and relationship of different pathological conditions within metabolic syndrome is still missing. New data on endocrine function of adipose tissue suggests that development and progression of atherosclerosis in this situation may be related to adipokines dysbalance. This study investigates correlation of leptin and adiponectin with clinical and laboratory changes in patients with metabolic disorders.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Ping Na Zhang ◽  
Meng Qi Zhou ◽  
Jing Guo ◽  
Hui Juan Zheng ◽  
Jingyi Tang ◽  
...  

Diabetic nephropathy (DN) is a progressive microvascular diabetic complication. Growing evidence shows that persistent mitochondrial dysfunction contributes to the progression of renal diseases, including DN, as it alters mitochondrial homeostasis and, in turn, affects normal kidney function. Pharmacological regulation of mitochondrial networking is a promising therapeutic strategy for preventing and restoring renal function in DN. In this review, we have surveyed recent advances in elucidating the mitochondrial networking and signaling pathways in physiological and pathological contexts. Additionally, we have considered the contributions of nontraditional therapy that ameliorate mitochondrial dysfunction and discussed their molecular mechanism, highlighting the potential value of nontraditional therapies, such as herbal medicine and lifestyle interventions, in therapeutic interventions for DN. The generation of new insights using mitochondrial networking will facilitate further investigations on nontraditional therapies for DN.


2021 ◽  
Vol 8 ◽  
Author(s):  
Taisiia Shemiakova ◽  
Ekaterina Ivanova ◽  
Wei-Kai Wu ◽  
Tatiana V. Kirichenko ◽  
Antonina V. Starodubova ◽  
...  

Atherosclerosis is a complex pathology that involves both metabolic dysfunction and chronic inflammatory process. During the last decade, a considerable progress was achieved in describing the pathophysiological features of atherosclerosis and developing approaches that target the abnormal lipid metabolism and chronic inflammation. However, early events in the arterial wall that initiate the disease development still remain obscure. Finding effective therapeutic targets in these early processes would allow developing methods for disease prevention and, possibly, atherosclerotic plaque regression. Currently, these early events are being actively studied by several research groups. One of the processes that are being investigated is the development of mitochondrial dysfunction, which was demonstrated to be present in the affected areas of the arterial wall. Detection and characterization of mitochondrial dysfunction associated with several chronic human disorders was made possible by the improved methods of studying mitochondrial biology and detecting mitochondrial DNA (mtDNA) mutations. It was found to be involved in several key atherogenic processes, such as oxidative stress, chronic inflammation, and intracellular lipid accumulation. Mitochondrial dysfunction can occur in all types of cells involved in the pathogenesis of atherosclerosis: monocytes and macrophages, smooth muscle cells, lymphocytes, and the endothelial cells. However, therapies that would specifically target the mitochondria to correct mitochondrial dysfunction and neutralize the defective organelles are still remain to be developed and characterized. The aim of this review is to outline the prospects for mitochondrial therapy for atherosclerosis. We discuss mechanisms of mitochondria-mediated atherogenic processes, known mitochondria-targeting therapy strategies, and novel mitochondria-targeting drugs in the context of atherosclerosis.


2020 ◽  
Vol 20 (1) ◽  
pp. 9-22
Author(s):  
Sergey A. Apryatin ◽  
Marina N. Karpenko ◽  
Zamira M. Muruzheva ◽  
Maria V. Bolshakova ◽  
Daria N. Magazenkova ◽  
...  

The aim of the study is the modern scientific literature estimation in the field of the investigation of neurodegenerative and metabolic disorders mediated by the trace amines and their receptors. The analysis of modern ideas about the feedback of neurodegenerative and metabolic diseases in which the trace amines and their receptors are involved was carried out. The important role of trace amines and their receptors in the regulation of the dopamine system, in connection with metabolic and neurodegenerative diseases, including Parkinsons disease, ADHD, schizophrenia, obesity, metabolic syndrome and other pathological conditions, has been shown. Trace amines and their receptors have a direct effect on dopamine systems, being regulators of various metabolic and neurodegenerative processes, participating in energy metabolism, neurogenesis, and other vital processes.


2019 ◽  
Vol 39 (4) ◽  
pp. 223-237 ◽  
Author(s):  
Muhammad Sajid Hamid Akash ◽  
Fareeha Fiayyaz ◽  
Kanwal Rehman ◽  
Shakila Sabir ◽  
Muhammad Hidayat Rasool

2020 ◽  
Vol 16 (6) ◽  
pp. 846-853
Author(s):  
Raghunandan Purohith ◽  
Nagendra P.M. Nagalingaswamy ◽  
Nanjunda S. Shivananju

Metabolic syndrome is a collective term that denotes disorder in metabolism, symptoms of which include hyperglycemia, hyperlipidemia, hypertension, and endothelial dysfunction. Diet is a major predisposing factor in the development of metabolic syndrome, and dietary intervention is necessary for both prevention and management. The bioactive constituents of food play a key role in this process. Micronutrients such as vitamins, carotenoids, amino acids, flavonoids, minerals, and aromatic pigment molecules found in fruits, vegetables, spices, and condiments are known to have beneficial effects in preventing and managing metabolic syndrome. There exists a well-established relationship between oxidative stress and major pathological conditions such as inflammation, metabolic syndrome, and cancer. Consequently, dietary antioxidants are implicated in the remediation of these complications. The mechanism of action and targets of dietary antioxidants as well as their effects on related pathways are being extensively studied and elucidated in recent times. This review attempts a comprehensive study of the role of dietary carotenoids in alleviating metabolic syndromewith an emphasis on molecular mechanism-in the light of recent advances.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Manjunath Ramanjaneya ◽  
Jayakumar Jerobin ◽  
Ilham Bettahi ◽  
Kodappully Sivaraman Siveen ◽  
Abdul-Badi Abou-Samra

AbstractObesity and insulin resistance are key elements of the metabolic syndrome, which includes type 2 diabetes (T2D), dyslipidemia, systemic inflammation, hypertension, elevated risk for cardiovascular diseases, non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS). C1Q Tumor necrosis factor-related proteins (CTRPs) have recently emerged as important regulators of metabolism as a core component in the interrelationship between insulin resistance, adiposity and inflammation. To date 15 CTRP members have been identified and most of the CTRPs are dysregulated in obesity, T2D, coronary artery disease and NAFLD. Pharmacological intervention and lifestyle modification alter expression of CTRPs in circulation and in metabolically active tissues. CTRPs enhance metabolism mainly through activation of AMPK/AKT dependent pathways and possess insulin sensitizing properties. Thus dysregulated expression of CTRPs in metabolic disorders could contribute to the pathogenesis of the disease. For these reasons CTRPs appear to be promising targets for early detection, prevention and treatment of metabolic disorders. This review article aims at exploring the role of CTRPs in metabolic syndrome.


2021 ◽  
Vol 10 (4) ◽  
pp. 835
Author(s):  
Manoja P. Herath ◽  
Jeffrey M. Beckett ◽  
Andrew P. Hills ◽  
Nuala M. Byrne ◽  
Kiran D. K. Ahuja

Exposure to untreated gestational diabetes mellitus (GDM) in utero increases the risk of obesity and type 2 diabetes in adulthood, and increased adiposity in GDM-exposed infants is suggested as a plausible mediator of this increased risk of later-life metabolic disorders. Evidence is equivocal regarding the impact of good glycaemic control in GDM mothers on infant adiposity at birth. We systematically reviewed studies reporting fat mass (FM), percent fat mass (%FM) and skinfold thicknesses (SFT) at birth in infants of mothers with GDM controlled with therapeutic interventions (IGDMtr). While treating GDM lowered FM in newborns compared to no treatment, there was no difference in FM and SFT according to the type of treatment (insulin, metformin, glyburide). IGDMtr had higher overall adiposity (mean difference, 95% confidence interval) measured with FM (68.46 g, 29.91 to 107.01) and %FM (1.98%, 0.54 to 3.42) but similar subcutaneous adiposity measured with SFT, compared to infants exposed to normal glucose tolerance (INGT). This suggests that IGDMtr may be characterised by excess fat accrual in internal adipose tissue. Given that intra-abdominal adiposity is a major risk factor for metabolic disorders, future studies should distinguish adipose tissue distribution of IGDMtr and INGT.


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