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mitochondrial disorders

Emine Sekerdag, Ihsan Solaroglu, Yasemin Gursoy-Ozdemir
As a result of ischemia or hemorrhage, blood supply to neurons is disrupted which subsequently promotes a cascade of pathophysiological responses resulting in cell loss. Many mechanisms are involved solely or in combination in this disorder including excitotoxicity, mitochondrial death pathways, and the release of free radicals, protein misfolding, apoptosis, necrosis, autophagy and inflammation. Besides neuronal cell loss, damage to and loss of astrocytes as well as injury to white matter contributes also to cerebral injury...
March 20, 2018: Current Neuropharmacology
Fernanda Silva Ferreira, Helena Biasibetti-Brendler, Paula Pierozan, Felipe Schmitz, Carolina Gessinger Bertó, Caroline Acauan Prezzi, Vanusa Manfredini, Angela T S Wyse
Kynurenic acid (KYNA) and quinolinic acid (QUIN) are metabolites produced in the degradation of tryptophan and have important neurological activities. KYNA/QUIN ratio changes are known to be associated with central nervous system disorders, such Alzheimer, Parkinson, and Huntington diseases. In the present study, we investigate the ability of KYNA in prevent the first events preceding QUIN-induced neurodegeneration in striatal slices of rat. We evaluated the protective effect of KYNA on oxidative status (reactive oxygen species production, antioxidant enzymes activities, lipid peroxidation, nitrite levels, protein and DNA damage, and iNOS immunocontent), mitochondrial function (mitochondrial mass, membrane potential, and respiratory chain enzymes), and Na+ ,K+ -ATPase in striatal slices of rats treated with QUIN...
March 21, 2018: Molecular Neurobiology
Lissette C Sánchez-Aranguren, Cindy T Espinosa-González, Laura M González-Ortiz, Sandra M Sanabria-Barrera, Carlos E Riaño-Medina, Andrés F Nuñez, Asif Ahmed, Jeannette Vasquez-Vivar, Marcos López
Preeclampsia is a maternal hypertensive disorder that affects up to 1 out of 12 pregnancies worldwide. It is characterized by proteinuria, endothelial dysfunction, and elevated levels of the soluble form of the vascular endothelial growth factor receptor-1 (VEGFR-1, known as sFlt-1). sFlt-1 effects are mediated in part by decreasing VEGF signaling. The direct effects of sFlt-1 on cellular metabolism and bioenergetics in preeclampsia, have not been established. The goal of this study was to evaluate whether sFlt-1 causes mitochondrial dysfunction leading to disruption of normal functioning in endothelial and placental cells in preeclampsia...
2018: Frontiers in Physiology
Wen Ding, Keyvan Yousefi, Stefania Goncalves, Bradley J Goldstein, Alfonso L Sabater, Amy Kloosterboer, Portia Ritter, Guerline Lambert, Armando J Mendez, Lina A Shehadeh
Alport syndrome is a rare hereditary renal disorder with no etiologic therapy. We found that osteopontin (OPN) is highly expressed in the renal tubules of the Alport mouse and plays a causative pathological role. OPN genetic deletion ameliorated albuminuria, hypertension, tubulointerstitial proliferation, renal apoptosis, and hearing and visual deficits in the Alport mouse. In Alport renal tubules we found extensive cholesterol accumulation and increased protein expression of dynamin-3 (DNM3) and LDL receptor (LDLR) in addition to dysmorphic mitochondria with defective bioenergetics...
March 22, 2018: JCI Insight
Jade Leahy, Schohraya Spahis, Eric Bonneil, Carole Garofalo, Guy Grimard, Sophia Morel, Caroline Laverdière, Maja Krajinovic, Simon Drouin, Edgard Delvin, Daniel Sinnett, Valérie Marcil, Emile Levy
BACKGROUND: Childhood acute lymphoblastic leukemia (cALL) is the most prevalent form of cancer in children. Due to advances in treatment and therapy, young cALL subjects now achieve a 90% survival rate. However, this tremendous advance does not come without consequence since ~2/3 of cALL survivors are affected by long-term and late, severe complications. Although the metabolic syndrome is a very serious sequel of cALL, the mechanisms remain undefined. It is also surprising to note that the mitochondrion, a central organelle in metabolic functions and the main cellular energy generator, have not yet been explored...
March 18, 2018: Metabolism: Clinical and Experimental
Noelia Morales-Prieto, Julia Ruiz-Laguna, David Sheehan, Nieves Abril
The use of DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane) in some countries, although regulated, is contributing to an increased worldwide risk of exposure to this organochlorine pesticide or its derivative p,p'-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene]. Many studies have associated p,p'-DDE exposure to type 2 diabetes, obesity and alterations of the reproductive system, but their molecular mechanisms of toxicity remain poorly understood. We have addressed this issue by using commercial microarrays based on probes for the entire Mus musculus genome to determine the hepatic transcriptional signatures of p,p'-DDE in the phylogenetically close mouse species Mus spretus...
March 16, 2018: Environmental Pollution
Kenji Yamada, Hideaki Shiraishi, Eishin Oki, Mika Ishige, Toshiyuki Fukao, Yusuke Hamada, Norio Sakai, Fumihiro Ochi, Asami Watanabe, Sanae Kawakami, Kazuyo Kuzume, Kenji Watanabe, Koji Sameshima, Kiyotaka Nakamagoe, Akira Tamaoka, Naoko Asahina, Saki Yokoshiki, Takashi Miyakoshi, Kota Ono, Koji Oba, Toshiyuki Isoe, Hiroshi Hayashi, Seiji Yamaguchi, Norihiro Sato
Introduction: Fatty acid oxidation disorders (FAODs) are rare diseases caused by defects in mitochondrial fatty acid oxidation (FAO) enzymes. While the efficacy of bezafibrate, a peroxisome proliferator-activated receptor agonist, on the in vitro FAO capacity has been reported, the in vivo efficacy remains controversial. Therefore, we conducted a clinical trial of bezafibrate in Japanese patients with FAODs. Materials and methods: This trial was an open-label, non-randomized, and multicenter study of bezafibrate treatment in 6 patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and 2 patients with carnitine palmitoyltransferase-II (CPT-2) deficiency (median age, 8...
June 2018: Molecular Genetics and Metabolism Reports
Xi Song, Qiyang Shen, Liting Fan, Qiuxiao Yu, Xiao Jia, Yu Sun, Wenpei Bai, Jihong Kang
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age and also an important metabolic disorder associated with insulin resistance (IR). Hyperandrogenism is a key feature of PCOS. However, whether hyperandrogenism can cause IR in PCOS remains largely unknown. The mammalian target of rapamycin complex 1 (mTORC1) and its regulated autophagy are closely associated with IR. In the present study, we investigated the role of mTORC1-autophagy pathway in skeletal muscle IR in a dehydroepiandrosterone (DHEA)-induced PCOS mouse model...
February 23, 2018: Oncotarget
Dan Wei, Ningning Zheng, Lanyan Zheng, Leting Wang, Liang Song, Luning Sun
Background: Metabolic syndrome (MS) is a global epidemic that has great socioeconomic and public health implications. This study reports observed effects of the Shexiang Baoxin Pill (SBP) in a rat model of MS and explores its underlying mechanisms of action. Methods: A diet-induced rat model of MS was established according to accepted methods, and the rats were randomly divided into two groups: a control group (0.9% NaCl, 100 mg/kg• d) and a SBP-treated group (SBP, 100 mg/kg• d). Systolic blood pressures, fasting blood glucose (FBS) levels, triglyceride (TG) levels, high-density lipoprotein cholesterol (HDL-C) levels, body weights, and abdominal perimeters were dynamically monitored and analyzed...
2018: Frontiers in Pharmacology
Varda Shoshan-Barmatz, Edna Nahon-Crystal, Anna Shteinfer-Kuzmine, Rajeev Gupta
Alzheimer's disease (AD) is an age-related neurodegenerative disorder. Although an accumulation of brain amyloid-β (Aβ) peptide and hyperphosphorylated tau protein have been implicated in the pathogenesis of AD, the etiology of the disease remains unclear. Mitochondrial dysfunction has been identified as an early event in AD pathogenesis and is reflected by reduced metabolism, disruption of Ca2+ homeostasis, and increased levels of reactive oxygen species, lipid peroxidation, and apoptosis. The focus of this review is the involvement of mitochondrial dysfunction in AD, and specifically, the role of the voltage-dependent anion channel 1 (VDAC1), which has been linked to AD pathogenesis...
March 15, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
María M Adeva-Andany, Natalia Carneiro-Freire, Mónica Seco-Filgueira, Carlos Fernández-Fernández, David Mouriño-Bayolo
Mitochondrial β-oxidation of fatty acids generates acetyl-coA, NADH and FADH2 . Acyl-coA synthetases catalyze the binding of fatty acids to coenzyme A to form fatty acyl-coA thioesters, the first step in the intracellular metabolism of fatty acids. l-carnitine system facilitates the transport of fatty acyl-coA esters across the mitochondrial membrane. Carnitine palmitoyltransferase-1 transfers acyl groups from coenzyme A to l-carnitine, forming acyl-carnitine esters at the outer mitochondrial membrane. Carnitine acyl-carnitine translocase exchanges acyl-carnitine esters that enter the mitochondria, by free l-carnitine...
March 15, 2018: Mitochondrion
Breann L Brown, Julia R Kardon, Robert T Sauer, Tania A Baker
5-Aminolevulinic acid synthase (ALAS) catalyzes the first step in heme biosynthesis. We present the crystal structure of a eukaryotic ALAS from Saccharomyces cerevisiae. In this homodimeric structure, one ALAS subunit contains covalently bound cofactor, pyridoxal 5'-phosphate (PLP), whereas the second is PLP free. Comparison between the subunits reveals PLP-coupled reordering of the active site and of additional regions to achieve the active conformation of the enzyme. The eukaryotic C-terminal extension, a region altered in multiple human disease alleles, wraps around the dimer and contacts active-site-proximal residues...
March 5, 2018: Structure
Navneet Ammal Kaidery, Bobby Thomas
Parkinson's disease (PD) is one of the most common neurodegenerative movement disorder characterized by preferential loss of dopaminergic neurons of the substantia nigra pars compacta and the presence of Lewy bodies containing α-synuclein. Although the cause of PD remains elusive, remarkable advances have been made in understanding the possible causative mechanisms of PD pathogenesis. An explosion of discoveries during the past two decades has led to the identification of several autosomal dominant and recessive genes that cause familial forms of PD...
March 14, 2018: Neurochemistry International
Daniele Orsucci, Gabriele Siciliano, Michelangelo Mancuso
No abstract text is available yet for this article.
March 9, 2018: EBioMedicine
Rui-Fang Wang, Guo-Fang Xue, Christian Hölscher, Miao-Jing Tian, Peng Feng, Ji-Ying Zheng, Dong-Fang Li
Glucagon-like peptide-1(GLP-1) is a growth factor that has neuroprotective and anti-inflammatory properties. The protease resistant GLP-1 analogue liraglutide has been shown to be neuroprotective in previous studies in animal models of Alzheimer's disease or Parkinson's disease. Status epilepticus (SE) is a complex disorder, involving many underlying pathological processes, including excitotoxic and chronic inflammatory events. The present pilot study aims to investigate whether liraglutide alleviates the chronic inflammation response and mitochondrial stress induced by SE in the lithium-pilocarpine animal model...
March 9, 2018: Epilepsy Research
Francesco Bellomo, Anna Signorile, Grazia Tamma, Marianna Ranieri, Francesco Emma, Domenico De Rasmo
Nephropathic cystinosis (NC) is a rare disease caused by mutations in the CTNS gene encoding for cystinosin, a lysosomal transmembrane cystine/H+ symporter, which promotes the efflux of cystine from lysosomes to cytosol. NC is the most frequent cause of Fanconi syndrome (FS) in young children, the molecular basis of which is not well established. Proximal tubular cells have very high metabolic rate due to the active transport of many solutes. Not surprisingly, mitochondrial disorders are often characterized by FS...
March 16, 2018: Cellular and Molecular Life Sciences: CMLS
Kalimuthusamy Natarajaseenivasan, Bianca Cotto, Santhanam Shanmughapriya, Alyssa A Lombardi, Prasun K Datta, Muniswamy Madesh, John W Elrod, Kamel Khalili, Dianne Langford
Calcium (Ca2+ ) dynamics and oxidative signaling control mitochondrial bioenergetics in the central nervous system, where astrocytes are a major energy source for neurons. Cocaine use exacerbates HIV-associated neurocognitive disorders, but little is known about disruptions in astrocyte metabolism in this context. Our data show that the HIV protein Tat and cocaine induce a metabolic switch from glucose to fatty acid oxidation in astrocytes, thereby limiting lactate transport to neurons. Mechanistic analyses revealed increased Mitochondrial Ca2+ Uniporter (MCU)-mediated Ca2+ uptake in astrocytes exposed to Tat and cocaine due to oxidation of MCU...
March 16, 2018: Cell Death & Disease
Jeffrey A Leibowitz, Brandi K Ormerod
A large proportion of Gulf War Veterans suffer from Gulf War Illness (GWI) - a devastating chronic disorder characterized by heterogeneous fatigue, pain and neuropsychological symptoms. In their recent Brain, Behavior and Immunity publication entitled "Curcumin Treatment Leads to Better Cognitive and Mood Function in a Model of Gulf War Illness with Enhanced Neurogenesis, and Alleviation of Inflammation and Mitochondrial Dysfunction in the Hippocampus", Kodali and colleagues (2018) report that the polyphenol curcumin improves cognition and mood in a rat model of GWI, potentially by increasing the expression of antioxidant genes and by reversing the effects of chronic combined acetylcholinesterase inhibitor exposure on neuroinflammation, mitochondrial respiration and hippocampal neurogenesis...
March 13, 2018: Brain, Behavior, and Immunity
Corina T Madreiter-Sokolowski, Armin A Sokolowski, Markus Waldeck-Weiermair, Roland Malli, Wolfgang F Graier
Senescence is related to the loss of cellular homeostasis and functions, which leads to a progressive decline in physiological ability and to aging-associated diseases. Since mitochondria are essential to energy supply, cell differentiation, cell cycle control, intracellular signaling and Ca2+ sequestration, fine-tuning mitochondrial activity appropriately, is a tightrope walk during aging. For instance, the mitochondrial oxidative phosphorylation (OXPHOS) ensures a supply of adenosine triphosphate (ATP), but is also the main source of potentially harmful levels of reactive oxygen species (ROS)...
March 16, 2018: Genes
Audrey M Bernstein, Robert Ritch, J Mario Wolosin
Exfoliation syndrome (XFS) is an age-related disease involving the deposition of aggregated fibrillar material (XFM) at extracellular matrices in tissues that synthesize elastic fibers. Its main morbidity is in the eye, where XFM accumulations form on the surface of the ciliary body, iris and lens. Exfoliation glaucoma (XFG) occurs in a high proportion of persons with XFS and can be a rapidly progressing disease. Worldwide, XFG accounts for about 25% of open-angle glaucoma cases. XFS and XFG show a sharp age-dependence, similarly to the many age-related diseases classified as aggregopathies...
March 15, 2018: Journal of Glaucoma
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