A5105370173- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- ATP Synthase and ATPases Research
- Coenzyme Q10 studies and effects
- Biochemical and Molecular Research
- Glycogen Storage Diseases and Myoclonus
- Advanced battery technologies research
- Genetic Neurodegenerative Diseases
- Neurogenetic and Muscular Disorders Research
- Muscle Physiology and Disorders
- RNA modifications and cancer
- Biochemical Acid Research Studies
- Genetics and Neurodevelopmental Disorders
- Cancer, Hypoxia, and Metabolism
- Cardiomyopathy and Myosin Studies
- Neurological diseases and metabolism
- Amyotrophic Lateral Sclerosis Research
- Nuclear Structure and Function
- Drug-Induced Ocular Toxicity
- Diet and metabolism studies
- RNA and protein synthesis mechanisms
- Chronic Lymphocytic Leukemia Research
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Autophagy in Disease and Therapy
Columbia University Irving Medical Center
2016-2025
Columbia University
2014-2024
Massachusetts General Hospital
1998-2023
Istituto delle Scienze Neurologiche di Bologna
2023
University of Bologna
2005-2023
Ferrari (Italy)
2008-2023
University of Milan
2023
Ospedale Maggiore
2023
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
2023
Daiichi Sankyo (United States)
2022
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive human disease associated with multiple deletions of skeletal muscle mitochondrial DNA (mtDNA), which have been ascribed to a defect in communication between the nuclear and genomes. Examination 12 MNGIE probands revealed homozygous or compound-heterozygous mutations gene specifying thymidine phosphorylase (TP), located on chromosome 22q13.32-qter. TP activity leukocytes from patients was less than 5...
Abstract We studied 23 patients with clinically defined mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes (MELAS), 25 oligosymptomatic or asymptomatic maternal relatives, 50 disease control subjects for the presence of a previously reported heteroplasmic point mutation at nt 3,243 in transfer RNA Leu(UUR) gene DNA. found high concordance between clinical diagnosis MELAS mutation, which was present 21 MELAS, all 11 12 14 but only five without MELAS. The proportion...
We studied the clinical, biochemical, and genetic features of eight patients with autosomal recessive mitochondrial syndrome neurogastrointestinal encephalomyopathy (MNGIE). MNGIE is clinically characterized by ophthalmoparesis, peripheral neuropathy, leukoencephalopathy, gastrointestinal symptoms (recurrent nausea, vomiting, or diarrhea) intestinal dysmotility, histologically abnormal mitochondria in muscle. Brain MRI scans were consistent leukodystrophy seven examined. Nerve conduction EMG...
<b>Objective: </b> To evaluate the efficacy of dichloroacetate (DCA) in treatment mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). <b>Background: High levels ventricular lactate, brain spectroscopic signature MELAS, correlate with more severe neurologic impairment. The authors hypothesized that chronic cerebral exacerbates neuronal injury MELAS therefore, investigated DCA, a potent lactate-lowering agent, as potential for MELAS. <b>Methods: conducted...
Coenzyme Q10 (CoQ10) deficiency is an autosomal recessive disorder with heterogenous phenotypic manifestations and genetic background. We describe seven patients from five independent families isolated myopathic phenotype of CoQ10 deficiency. The clinical, histological biochemical presentation our was very homogenous. All presented exercise intolerance, fatigue, proximal myopathy high serum CK. Muscle histology showed lipid accumulation subtle signs mitochondrial myopathy. Biochemical...
Mitochondrial disorders represent a large collection of rare syndromes that are difficult to manage both because we do not fully understand biochemical pathogenesis and currently lack facile markers severity. The m.3243A>G variant is the most common heteroplasmic mitochondrial DNA mutation underlies spectrum diseases, notably encephalomyopathy lactic acidosis stroke-like episodes (MELAS). To identify robust circulating disease, first performed discovery proteomics, targeted metabolomics,...
Abstract Patients with primary mitochondrial oxidative phosphorylation (OxPhos) defects present fatigue and multi-system disorders, are often lean, die prematurely, but the mechanistic basis for this clinical picture remains unclear. By integrating data from 17 cohorts of patients diseases ( n = 690) we find evidence that these disorders increase resting energy expenditure, a state termed hypermetabolism . We examine phenomenon longitudinally in patient-derived fibroblasts multiple donors....
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder defined clinically by severe gastrointestinal dysmotility; cachexia; ptosis, ophthalmoparesis, or both; peripheral neuropathy; leukoencephalopathy; and mitochondrial abnormalities. The disease caused mutations in the thymidine phosphorylase (TP) gene. TP protein catalyzes phosphorolysis of to thymine deoxyribose 1-phosphate. We identified 21 probands (35 patients) who fulfilled our clinical...
Dysfunction of mitochondrial complex I is a feature human neurodegenerative diseases such as Leber hereditary optic neuropathy and Parkinson's disease. This defect associated with recruitment the mitochondrial-dependent apoptotic pathway in vivo . However, isolated brain mitochondria, dysfunction caused by either pharmacological or genetic means fails to directly activate this cell death pathway. Instead, deficits stimulate intramitochondrial oxidative stress, which, turn, increase...