Pathogenic mechanisms underlying spinocerebellar ataxia type 1.

Pathogenic mechanisms underlying spinocerebellar ataxia type 1. Cell Mol Life Sci. 2020 Apr 18;: Authors: Tejwani L, Lim J Abstract The family of hereditary cerebellar ataxias is a large group of disorders with heterogenous clinical manifestations and genetic etiologies. Among these, over 30 autosomal dominantly inherited subtypes have been identified, collectively referred to as the spinocerebellar ataxias (SCAs). Generally, the SCAs are characterized by a progressive gait impairment with classical cerebellar features, and in a subset of SCAs, accompanied by extra-cerebellar features. Beyond the common gait impairment and cerebellar atrophy, the wide range of additional clinical features observed across the SCAs is likely explained by the diverse set of mutated genes that encode proteins with seemingly disparate functional roles in nervous system biology. By synthesizing knowledge obtained from studies of the various SCAs over the past several decades, convergence onto a few key cellular changes, namely ion channel dysfunction and transcriptional dysregulation, has become apparent and may represent central mechanisms of cerebellar disease pathogenesis. This review will detail our current understanding of the molecular pathogenesis of the SCAs, focusing primarily on the first described autosomal dominant spinocerebellar ataxia, SCA1, as well as the emerging common core mechanisms across the various SCAs. PMID: 32306062 [PubMed - as supplied by publi...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research

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Authors: Schep LJ, Slaughter RJ, Glue P, Gee P Abstract Cannabis is one of the most widely used recreational drugs in the world. Tetrahydrocannabinol (THC) is the psychoactive principal constituent of the cannabis plant (Cannabis sativa). It is taken either orally or by inhalation, resulting in sedation, euphoria, relaxation and loss of social inhibition. Adverse effects from higher doses can include fear, distrust and a profound state of unease, hallucinations, ataxia, stupor and seizures. Long-term use can result in respiratory and cardiovascular toxicity and has been associated with a range of psychiatric condit...
Source: New Zealand Medical Journal - Category: General Medicine Tags: N Z Med J Source Type: research
The outbreak of Coronavirus disease 2019 (COVID-19) has been widely reported to cause symptoms such as fever, cough, sore throat, fatigue and shortness of breath. Neurological complications have not been widely reported without associated respiratory symptoms. These neurological manifestations have been found mostly in the elderly1. There has been no report of ataxia or COVID-19 cerebellitis in the young adult population without associated respiratory symptoms.
Source: The Journal of Emergency Medicine - Category: Emergency Medicine Authors: Tags: Selected Topics: Neurological Emergencies Source Type: research
In conclusion, these bioinformatic data uncovered the network targets and mechanisms of calycosin-anti-meningitis. And the current findings indicated that the vital targets might be used as potent biomarkers for detecting meningitis. PMID: 33031061 [PubMed - as supplied by publisher]
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
This article reviews cardiovascular problems in premutation carriers and discusses possible contributing mechanisms including RNA toxicity and mild fragile X mental retardation protein deficiency. Further research studies are needed in order to prove a direct association of the cardiovascular problems in fragile X premutation carriers because such knowledge will lead to better preventative treatment.
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
ABSTRACT Autosomal dominant cerebellar ataxias (ADCA) are heterogeneous diseases with a highly variable phenotype and genotype. They can be divided into episodic ataxia and spinocerebellar ataxia (SCA); the latter is considered the prototype of the ADCA. Most of the ADCA are caused by polyglutamine expansions, mainly SCA 1, 2, 3, 6, 7, 17 and Dentatorubral-pallidoluysian atrophy (DRPLA). However, 30% of patients remain undiagnosed after testing for these most common SCA. Recently, several studies have demonstrated that the new generation of sequencing methods are useful for the diagnose of these patients. This review focus...
Source: Arquivos de Neuro-Psiquiatria - Category: Neurology Source Type: research
CONCLUSION: In conclusion, we report a novel variant in CWF19L1 as a candidate causal variant in two sisters with autosomal recessive cerebellar ataxia. This is the first report coming from Arab countries. Additional reports in patients with a progressive course and adult-onset are needed, but this could be the first report of this disease diagnosed in adulthood since it is a disease of children and adolescents. In addition, our patients had epileptic seizures, which were not previously documented in patients with CWF19L1 mutations. We postulate that mutations in this gene have widespread functional and structural changes ...
Source: Neurological Research - Category: Neurology Tags: Neurol Res Source Type: research
It is thought that the brain does not simply react to sensory feedback, but rather uses an internal model of the body to predict the consequences of motor commands before sensory feedback arrives. Time-delayed sensory feedback can then be used to correct for the unexpected —perturbations, motor noise, or a moving target. The cerebellum has been implicated in this predictive control process. Here we show that the feedback gain in patients with cerebellar ataxia matches that of healthy subjects, but that patients exhibit substantially more phase lag. This difference i s captured by a computational model incorporating a...
Source: eLife - Category: Biomedical Science Tags: Neuroscience Source Type: research
Condition:   Friedreich Ataxia Interventions:   Drug: Vatiquinone;   Drug: Placebo Sponsor:   PTC Therapeutics Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
ConclusionsHistological changes of the arachnoid correlate with preoperative symptoms. Relationships between arachnoid and surrounding tissues show even higher correlations with predictive power for short- and long-term outcomes. These findings suggest a pathophysiological role for the arachnoid in Chiari I malformation.
Source: Acta Neurochirurgica - Category: Neurosurgery Source Type: research
AbstractWhile rehabilitation therapies always help patients with ataxia, there are currently no FDA-approved treatments for ataxia. Medications are available to treat symptoms that may complicate an ataxic illness, e.g., tremor, myoclonus, dystonia, and rigidity, which are discussed elsewhere in this volume. Spasticity, pain, fatigue, depression, sleep disturbances, cognitive decline, and bowel and bladder dysfunction, if they occur, all have multiple available drugs and therapies for symptomatic use. There is also an extensive literature on off-label uses of various medications to improve imbalance. The pipeline of emergi...
Source: Neurotherapeutics - Category: Neurology Source Type: research
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