Search results for " atrophy"
showing 10 items of 209 documents
Exome sequencing in congenital ataxia identifies two new candidate genes and highlights a pathophysiological link between some congenital ataxias and…
2019
To investigate the genetic basis of congenital ataxias (CAs), a unique group of cerebellar ataxias with a nonprogressive course, in 20 patients from consanguineous families, and to identify new CA genes. Singleton -exome sequencing on these 20 well-clinically characterized CA patients. We first checked for rare homozygous pathogenic variants, then, for variants from a list of genes known to be associated with CA or very early-onset ataxia, regardless of their mode of inheritance. Our replication cohort of 180 CA patients was used to validate the new CA genes. We identified a causal gene in 16/20 families: six known CA genes (7 patients); four genes previously implicated in another neurologi…
Autosomal-Recessive Mutations in AP3B2, Adaptor-Related Protein Complex 3 Beta 2 Subunit, Cause an Early-Onset Epileptic Encephalopathy with Optic At…
2016
International audience; Early-onset epileptic encephalopathy (EOEE) represents a heterogeneous group of severe disorders characterized by seizures, interictal epileptiform activity with a disorganized electroencephalography background, developmental regression or retardation, and onset before 1 year of age. Among a cohort of 57 individuals with epileptic encephalopathy, we ascertained two unrelated affected individuals with EOEE associated with developmental impairment and autosomal-recessive variants in AP3B2 by means of whole-exome sequencing. The targeted sequencing of AP3B2 in 86 unrelated individuals with EOEE led to the identification of an additional family. We gathered five addition…
Vascular Risk Factors, Vascular Diseases, and Imaging Findings in a Hospital-based Cohort of Mild Cognitive Impairment Types
2017
Background: Mild Cognitive Impairment (MCI) is a transitional state between normal cognition and dementia. Objective: The aim of this study is to investigate the role of vascular risk factors, vascular diseases, cerebrovascular disease and brain atrophy in a large hospital-based cohort of MCI types including 471 amnestic MCI (a-MCI), 693 amnestic MCI multiple domain (a-MCImd), 322 single non-memory MCI (snm-MCI), and 202 non amnestic MCI multiple domain (na-MCImd). For comparison, 1,005 neurologically and cognitively healthy subjects were also evaluated. Method: Several vascular risk factors and vascular diseases were assessed. All participants underwent neurological, neuropsychological an…
Drosophila SMN2minigene reporter model identifies moxifloxacin as a candidate therapy for SMA
2018
Spinal muscular atrophy is a rare and fatal neuromuscular disorder caused by the loss of alpha motor neurons. The affected individuals have mutated the ubiquitously expressed SMN1 gene resulting in the loss or reduction in the survival motor neuron (SMN) protein levels. However, an almost identical paralog exists in humans: SMN2. Pharmacological activation of SMN2 exon 7 inclusion by small molecules or modified antisense oligonucleotides is a valid approach to treat SMA. Here we describe an in vivo SMN2 minigene reporter system in Drosophila motor neurons that serves as a cost-effective, feasible, and stringent primary screening model for identifying chemicals capable of crossing the conser…
Morphological Evidence of Telocytes in Skeletal Muscle Interstitium of Exercised and Sedentary Rodents
2021
Skeletal muscle atrophy, resulting from states of hypokinesis or immobilization, leads to morphological, metabolic, and functional changes within the muscle tissue, a large variety of which are supported by the stromal cells populating the interstitium. Telocytes represent a recently discovered population of stromal cells, which has been increasingly identified in several human organs and appears to participate in sustaining cross-talk, promoting regenerative mechanisms and supporting differentiation of local stem cell niche. The aim of this morphologic study was to investigate the presence of Telocytes in the tibialis anterior muscle of healthy rats undergoing an endurance training protoco…
An update on intracerebral stem cell grafts.
2018
Introduction: Primary neurological disorders are notoriously debilitating and deadly, and over the past four decades stem cell therapy has emerged as a promising treatment. Translation of stem cell therapies from the bench to the clinic requires a better understanding of delivery protocols, safety profile, and efficacy in each disease. Areas covered: In this review, benefits and risks of intracerebral stem cell transplantation are presented for consideration. Milestone discoveries in stem cell applications are reviewed to examine the efficacy and safety of intracerebral stem cell transplant therapy for disorders of the central nervous system and inform design of translatable protocols for c…
Lon protease: a novel mitochondrial matrix protein in the interconnection between drug-induced mitochondrial dysfunction and endoplasmic reticulum st…
2017
Background and Purpose Mitochondria-associated membranes (MAMs) are specific endoplasmic reticulum (ER) domains that enable it to interact directly with mitochondria and mediate metabolic flow and Ca2+ transfer. A growing list of proteins have been identified as MAMs components, but how they are recruited and function during complex cell stress situations is still not understood, while the participation of mitochondrial matrix proteins is largely unrecognized. Experimental Approach This work compares mitochondrial/ER contact during combined ER stress/mitochondrial dysfunction using a model of human hepatoma cells (Hep3B cell line) treated for 24 h with classic pharmacological inducers of ER…
Allopurinol partially prevents disuse muscle atrophy in mice and humans
2018
AbstractDisuse muscle wasting will likely affect everyone in his or her lifetime in response to pathologies such as joint immobilization, inactivity or bed rest. There are no good therapies to treat it. We previously found that allopurinol, a drug widely used to treat gout, protects muscle damage after exhaustive exercise and results in functional gains in old individuals. Thus, we decided to test its effect in the prevention of soleus muscle atrophy after two weeks of hindlimb unloading in mice, and lower leg immobilization following ankle sprain in humans (EudraCT: 2011-003541-17). Our results show that allopurinol partially protects against muscle atrophy in both mice and humans. The pro…
MicroRNAs Dysregulation and Metabolism in Multiple System Atrophy.
2019
Multiple system atrophy (MSA) is an adult onset, fatal disease, characterized by an accumulation of alpha-synuclein (α-syn) in oligodendroglial cells. MicroRNAs (miRNAs) are small non-coding RNAs involved in post-translational regulation and several biological processes. Disruption of miRNA-related pathways in the central nervous system (CNS) plays an important role in the pathogenesis of neurodegenerative diseases, including MSA. While the exact mechanisms underlying miRNAs in the pathogenesis of MSA remain unclear, it is known that miRNAs can repress the translation of messenger RNAs (mRNAs) that regulate the following pathogenesis associated with MSA: autophagy, neuroinflammation, α-syn …
Automated Categorization of Parkinsonian Syndromes Using Magnetic Resonance Imaging in a Clinical Setting
2020
Background Machine learning algorithms using magnetic resonance imaging (MRI) data can accurately discriminate parkinsonian syndromes. Validation in patients recruited in routine clinical practice is missing. Objective The aim of this study was to assess the accuracy of a machine learning algorithm trained on a research cohort and tested on an independent clinical replication cohort for the categorization of parkinsonian syndromes. Methods Three hundred twenty-two subjects, including 94 healthy control subjects, 119 patients with Parkinson's disease (PD), 51 patients with progressive supranuclear palsy (PSP) with Richardson's syndrome, 35 with multiple system atrophy (MSA) of the parkinsoni…