P.63Chronic progressive external ophthalmoplegia (CPEO) and CPEO-plus cohort of 54 patients from the Netherlands

Chronic progressive ophthalmoplegia (CPEO) is a mitochondrial disease. It is part of a spectrum of mitochondrial DNA deletion disorders. In CPEO, by definition, the eye muscles are affected, causing eye movement deficits and ptosis. Phenotypes with further neurologic involvement are often described as CPEO-plus. Other phenotypes within the spectrum are well defined, such as Sensory Ataxia, Neuropathy, Dysarthria and Ophthalmoplegia (SANDO)-syndrome or Kearns-Sayre syndrome. In the future, well defined diagnostic criteria are essential for clinical trials.
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research

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AbstractNeurometabolic disorders are often inherited and complex disorders that result from abnormalities of enzymes important for development and function of the nervous system. Recently, biallelic mutations inNAXE (APOA1BP) were found in patients with an infantile, lethal, neurometabolic disease. Here, exome sequencing was performed in two affected sisters and their healthy parents. The best candidate,NAXE, was tested for replication in exome sequencing data from 4351 patients with neurodevelopmental disorders. Quantitative RT-PCR, western blot and form factor analysis were performed to assessNAXE expression, protein lev...
Source: Journal of Neurology - Category: Neurology Source Type: research
In this study, oxidative stress, DNA damage, and cell apoptosis were increased after METH exposure, and the expressions of DNA repair-associated proteins, including the phosphorylation of ataxia telangiectasia mutant (p-ATM) and checkpoint kinase 2 (p-Chk2), significantly declined in PC12 cells after high-dose or long-time METH treatment. Additionally, tea polyphenols could protect PC12 cells against METH-induced cell viability loss, reactive oxide species and nitric oxide production, and mitochondrial dysfunction and suppress METH-induced apoptosis. Furthermore, tea polyphenols could increase the antioxidant capacities an...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Publication date: Available online 23 November 2019Source: Molecular and Cellular NeuroscienceAuthor(s): Anna Stepanova, Jordi MagranéAbstractFriedreich's ataxia is a multisystemic genetic disorder within the family of mitochondrial diseases that is characterized by reduced levels of the essential mitochondrial protein frataxin. Based on clinical evidence, the peripheral nervous system is affected early, neuronal dysfunction progresses towards the central nervous system, and other organs (such as heart and pancreas) are affected later. However, little attention has been given to the specific aspects of mitochondria ...
Source: Molecular and Cellular Neuroscience - Category: Neuroscience Source Type: research
We report a 39-year old female presenting with childhood-onset and progressive neuroophthalmic manifestation with optic atrophy, mixed polyneuropathy, spinal and cerebellar ataxia and generalized chorea associated with mtDNA depletion. Whole-exome sequencing identified an ultra-rare homozygous missense mutation located at Chr17: 062474101-C > A (p.Asp433Tyr) in nuclear POLG2 gene encoding PolγB, an accessory subunits of mitochondrial polymerase γ responsible for mtDNA replication. The healthy parents and 2 sisters of the patient were heterozygous for the variant. To our best knowledge, this is the first ...
Source: European Journal of Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Eur J Med Genet Source Type: research
Publication date: December 2019Source: Molecular Genetics and Metabolism Reports, Volume 21Author(s): Konstantina Fragaki, Annabelle Chaussenot, Valerie Serre, Cecile Acquaviva, Sylvie Bannwarth, Cecile Rouzier, Brigitte Chabrol, Veronique Paquis-FlucklingerAbstractAmong mitochondrial diseases, isolated complex V (CV) deficiency represents a rare cause of respiratory chain (RC) dysfunction. In mammalian mitochondrial DNA (mtDNA), MT-ATP6 partly overlaps with MT-ATP8 making double mutations possible, yet extremely rarely reported principally in patients with cardiomyopathy. Here, we report a novel m.8561 C>T substitution...
Source: Molecular Genetics and Metabolism Reports - Category: Genetics & Stem Cells Source Type: research
This article presents the original descriptions of some recent physics mechanisms (based on the thermodynamic, kinetic, and quantum tunnel effects) providing stable 2H/1H isotope fractionation, leading to the accumulation of particular isotopic forms in intra- or intercellular space, including the molecular effects of deuterium interaction with 18O/17O/16O, 15N/14N, 13C/12C, and other stable biogenic isotopes. These effects were observed mainly at the organelle (mitochondria) and cell levels. A new hypothesis for heavy nonradioactive isotope fractionation in living systems via neutron effect realization is discussed. The c...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
We present a sibling pair: one with cerebellar ataxia and one with vision loss and cognitive impairment in addition to ataxia. Neither shows evidence of leukoencephalopathy on MRI imaging. Exome sequencing revealed that both siblings are compound heterozygous forAARS2 variants (p.Phe131del and p.Ile328Met). Yeast complementation assays indicate that p.Phe131delAARS2 dramatically impairs gene function and that p.Ile328MetAARS2 is a hypomorphic allele. This work expands the phenotypic spectrum ofAARS2-associated disease to include ataxia without leukoencephalopathy.
Source: The Cerebellum - Category: Neurology Source Type: research
We present a sibling pair: one with cerebellar ataxia and one with vision loss and cognitive impairment in addition to ataxia. Neither shows evidence of leukoencephalopathy on MRI imaging. Exome sequencing revealed that both siblings are compound heterozygous for AARS2 variants (p.Phe131del and p.Ile328Met). Yeast complementation assays indicate that p.Phe131del AARS2 dramatically impairs gene function and that p.Ile328Met AARS2 is a hypomorphic allele. This work expands the phenotypic spectrum of AARS2-associated disease to include ataxia without leukoencephalopathy. PMID: 31705293 [PubMed - as supplied by publisher]
Source: Cerebellum - Category: Neuroscience Authors: Tags: Cerebellum Source Type: research
In conclusion, a polypharmacology approach of combining established, prolongevity drug inhibitors of specific nodes may be the most effective way to target the nutrient-sensing network to improve late-life health. Deletion of p38α in Neurons Slows Neural Stem Cell Decline and Loss of Cognitive Function in Mice https://www.fightaging.org/archives/2019/10/deletion-of-p38%ce%b1-in-neurons-slows-neural-stem-cell-decline-and-loss-of-cognitive-function-in-mice/ Researchers here provide evidence for p38α to be involved in the regulation of diminished neural stem cell activity with age. It is thought...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
ConclusionsWe describe a unique and novel cellular model that provides insight into the mitochondrial abnormalities present in DCMA and identifies SS-31 as a potential therapeutic for this devastating disease.
Source: Canadian Journal of Cardiology - Category: Cardiology Source Type: research
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