The genetic nomenclature of recessive cerebellar ataxias

2018 ◽  
Vol 33 (7) ◽  
pp. 1056-1076 ◽  
Author(s):  
Malco Rossi ◽  
Mathieu Anheim ◽  
Alexandra Durr ◽  
Christine Klein ◽  
Michel Koenig ◽  
...  
Keyword(s):  
Genetic Nomenclature ◽  
Cerebellar Ataxias

Neurotransplantation Therapy and Cerebellar Reserve

2018 ◽  
Vol 17 (3) ◽  
pp. 172-183 ◽  
Author(s):  
Jan Cendelin ◽  
Hiroshi Mitoma ◽  
Mario Manto
Keyword(s):  
Neural Plasticity ◽  
Clinical Evidence ◽  
The Self ◽  
Regenerative Processes ◽  
Recovery Capacity ◽  
Cerebellar Ataxias ◽  
Synaptic Formation ◽  
Target Recovery ◽  
Cerebellar Anatomy ◽  
Functional Circuitry

Background & Objective: Neurotransplantation has been recently the focus of interest as a promising therapy to substitute lost cerebellar neurons and improve cerebellar ataxias. However, since cell differentiation and synaptic formation are required to obtain a functional circuitry, highly integrated reproduction of cerebellar anatomy is not a simple process. Rather than a genuine replacement, recent studies have shown that grafted cells rescue surviving cells from neurodegeneration by exerting trophic effects, supporting mitochondrial function, modulating neuroinflammation, stimulating endogenous regenerative processes, and facilitating cerebellar compensatory properties thanks to neural plasticity. On the other hand, accumulating clinical evidence suggests that the self-recovery capacity is still preserved even if the cerebellum is affected by a diffuse and progressive pathology. We put forward the period with intact recovery capacity as “restorable stage” and the notion of reversal capacity as “cerebellar reserve”. Conclusion: The concept of cerebellar reserve is particularly relevant, both theoretically and practically, to target recovery of cerebellar deficits by neurotransplantation. Reinforcing the cerebellar reserve and prolonging the restorable stage can be envisioned as future endpoints of neurotransplantation.

High efficiency and clinical relevance of exome sequencing in the daily practice of neurogenetics

2021 ◽  
pp. jmedgenet-2020-107369
Author(s):  
Quentin Thomas ◽  
Antonio Vitobello ◽  
Frederic Tran Mau-Them ◽  
Yannis Duffourd ◽  
Agnès Fromont ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Neurological Disorders ◽  
High Efficiency ◽  
Neuromuscular Disorders ◽  
Daily Practice ◽  
Pathogenic Variants ◽  
Complex Phenotypes ◽  
Cerebellar Ataxias ◽  
Mitochondrial Origin ◽  
Second Tier

ObjectiveTo assess the efficiency and relevance of clinical exome sequencing (cES) as a first-tier or second-tier test for the diagnosis of progressive neurological disorders in the daily practice of Neurology and Genetic Departments.MethodsSixty-seven probands with various progressive neurological disorders (cerebellar ataxias, neuromuscular disorders, spastic paraplegias, movement disorders and individuals with complex phenotypes labelled ‘other’) were recruited over a 4-year period regardless of their age, gender, familial history and clinical framework. Individuals could have had prior genetic tests as long as it was not cES. cES was performed in a proband-only (60/67) or trio (7/67) strategy depending on available samples and was analysed with an in-house pipeline including software for CNV and mitochondrial-DNA variant detection.ResultsIn 29/67 individuals, cES identified clearly pathogenic variants leading to a 43% positive yield. When performed as a first-tier test, cES identified pathogenic variants for 53% of individuals (10/19). Difficult cases were solved including double diagnoses within a kindred or identification of a neurodegeneration with brain iron accumulation in a patient with encephalopathy of suspected mitochondrial origin.ConclusionThis study shows that cES is a powerful tool for the daily practice of neurogenetics offering an efficient (43%) and appropriate approach for clinically and genetically complex and heterogeneous disorders.

scholarly journals Beneficial Effects of Acetyl-DL-Leucine (ADLL) in a Mouse Model of Sandhoff Disease

2020 ◽  
Vol 9 (4) ◽  
pp. 1050 ◽  
Author(s):  
Ecem Kaya ◽  
David A. Smith ◽  
Claire Smith ◽  
Barry Boland ◽  
Michael Strupp ◽  
...  
Keyword(s):  
Mouse Model ◽  
Sandhoff Disease ◽  
Lysosomal Storage ◽  
Gm2 Ganglioside ◽  
Beneficial Effects ◽  
New Therapeutic Approaches ◽  
Late Endosomes ◽  
Altered Glucose ◽  
Cerebellar Ataxias ◽  
Niemann Pick

Sandhoff disease is a rare neurodegenerative lysosomal storage disease associated with the storage of GM2 ganglioside in late endosomes/lysosomes. Here, we explored the efficacy of acetyl-DL-leucine (ADLL), which has been shown to improve ataxia in observational studies in patients with Niemann–Pick Type C1 and other cerebellar ataxias. We treated a mouse model of Sandhoff disease (Hexb-/-) (0.1 g/kg/day) from 3 weeks of age with this orally available drug. ADLL produced a modest but significant increase in life span, accompanied by improved motor function and reduced glycosphingolipid (GSL) storage in the forebrain and cerebellum, in particular GA2. ADLL was also found to normalize altered glucose and glutamate metabolism, as well as increasing autophagy and the reactive oxygen species (ROS) scavenger, superoxide dismutase (SOD1). Our findings provide new insights into metabolic abnormalities in Sandhoff disease, which could be targeted with new therapeutic approaches, including ADLL.

scholarly journals Guidelines for Genetic Nomenclature and Community Governance for the Model Legume Medicago truncatula

2001 ◽  
Vol 14 (12) ◽  
pp. 1364-1367 ◽  
Author(s):  
Kathryn A. VandenBosch ◽  
Julia Frugoli
Keyword(s):  
Medicago Truncatula ◽  
Rapid Growth ◽  
Model System ◽  
Gene Nomenclature ◽  
Community Governance ◽  
Model Legume ◽  
The Past ◽  
Genetic Nomenclature ◽  
International Collaborations

At the 2nd Medicago meeting (a satellite of the 1999 IS-MPMI meeting in Amsterdam), investigators perceived a need for standardization of genetic nomenclature in Medicago truncatula, due to the rapid growth of research on this species in the past few years. Establishment of such standards grew out of discussions begun at this meeting and continued electronically throughout the M. truncatula community. The proposed standards presented here are the consensus results of those discussions. In addition to standards for gene nomenclature, a method for community governance and a website for cataloging gene names and submitting new ones are presented. The purpose of implementing these guidelines is to help maintain consistency in the literature, to avoid redundancy, to contribute to the accuracy of databases, and, in general, to aid the international collaborations that have made M. truncatula a model system for legume biology.

scholarly journals Protective Effect of Memantine on Bergmann Glia and Purkinje Cells Morphology in Optogenetic Model of Neurodegeneration in Mice

2021 ◽  
Vol 22 (15) ◽  
pp. 7822
Author(s):  
Anton N. Shuvaev ◽  
Olga S. Belozor ◽  
Oleg I. Mozhei ◽  
Elena D. Khilazheva ◽  
Andrey N. Shuvaev ◽  
...  
Keyword(s):  
Excitatory Amino Acid ◽  
Average Length ◽  
Glutamate Transporter ◽  
Bergmann Glia ◽  
Spinocerebellar Ataxias ◽  
Excitatory Amino Acid Transporter ◽  
Glial Glutamate Transporter ◽  
Gfap Immunoreactivity ◽  
Cerebellar Ataxias ◽  
Receptor Blockers

Spinocerebellar ataxias are a family of fatal inherited diseases affecting the brain. Although specific mutated proteins are different, they may have a common pathogenetic mechanism, such as insufficient glutamate clearance. This function fails in reactive glia, leading to excitotoxicity and overactivation of NMDA receptors. Therefore, NMDA receptor blockers could be considered for the management of excitotoxicity. One such drug, memantine, currently used for the treatment of Alzheimer’s disease, could potentially be used for the treatment of other forms of neurodegeneration, for example, spinocerebellar ataxias (SCA). We previously demonstrated close parallels between optogenetically induced cerebellar degeneration and SCA1. Here we induced reactive transformation of cerebellar Bergmann glia (BG) using this novel optogenetic approach and tested whether memantine could counteract changes in BG and Purkinje cell (PC) morphology and expression of the main glial glutamate transporter—excitatory amino acid transporter 1 (EAAT1). Reactive BG induced by chronic optogenetic stimulation presented increased GFAP immunoreactivity, increased thickness and decreased length of its processes. Oral memantine (~90 mg/kg/day for 4 days) prevented thickening of the processes (1.57 to 1.81 vs. 1.62 μm) and strongly antagonized light-induced reduction in their average length (186.0 to 150.8 vs. 171.9 μm). Memantine also prevented the loss of the key glial glutamate transporter EAAT1 on BG. Finally, memantine reduced the loss of PC (4.2 ± 0.2 to 3.2 ± 0.2 vs. 4.1 ± 0.3 cells per 100 μm of the PC layer). These results identify memantine as potential neuroprotective therapeutics for cerebellar ataxias.

Proposed Genetic Nomenclature Rules for Tetrahymena thermophila, Paramecium primaurelia and Paramecium tetraurelia

Genetics ◽  
1998 ◽  
Vol 149 (1) ◽  
pp. 459-462 ◽  
Author(s):  
◽  
Sally Lyman Allen ◽  
Marsha I Altschuler ◽  
Peter J Bruns ◽  
Jean Cohen ◽  
...  
Keyword(s):  
Tetrahymena Thermophila ◽  
Ciliated Protozoa ◽  
Paramecium Tetraurelia ◽  
Short Introduction ◽  
Genetic Nomenclature

Abstract The genetics of the ciliated protozoa Tetrahymena thermophila and certain species of Paramecium (P. primaurelia and P. tetraurelia) have reached a level of maturity such that rules for genetic nomenclature for micronuclear and macronuclear genetics need to be clarified for workers in the field as well as for other geneticists. After a short introduction, the rules follow.

scholarly journals Autosomal Recessive Cerebellar Ataxias: Paving the Way toward Targeted Molecular Therapies

Neuron ◽  
2019 ◽  
Vol 101 (4) ◽  
pp. 560-583 ◽  
Author(s):  
Matthis Synofzik ◽  
Hélène Puccio ◽  
Fanny Mochel ◽  
Ludger Schöls
Keyword(s):  
Autosomal Recessive ◽  
Cerebellar Ataxias ◽  
Molecular Therapies ◽  
Targeted Molecular Therapies ◽  
Autosomal Recessive Cerebellar Ataxias ◽  
The Way
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