Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Target Concepts:
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Query: UMLS:C0016719 (
Friedreich's ataxia
)
2,098
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Ataxia with vitamin E deficiency (AVED) is a rare autosomal recessive neurodegenerative disease, due to mutations in TTPA gene (Arita et al. in Biochem J 306(Pt. 2):437-443, 1995; Hentati et al. in Ann Neurol 39:295-300, 1996), which encodes for alpha-TTP, a cytosolic liver protein that is presumed to function in the intracellular transport of alpha-tocopherol. This disease is characterized clinically by symptoms with often striking resemblance to those of
Friedreich ataxia
. The neurological symptoms include ataxia, dysarthria, hyporeflexia, and decreased vibration sense, sometimes associated with cardiomyopathy and retinitis pigmentosa (Mariotti et al. in Neurol Sci 25:130-137, 2004).
Vitamin E
supplementation improves symptoms and prevents disease progress (Doria-Lamba et al. in Eur J Pediatr 165(7):494-495, 2006). Over 20 mutations have been identified in patients with AVED. In the present paper we summarize the recent findings on molecular genetic of this disease including the list of the known mutations.
...
PMID:Ataxia with vitamin E deficiency: update of molecular diagnosis. 2046 73
Vitamin E
(alpha-and gamma-tocopherol) may slow the progression of a number of major degenerative diseases of the nervous system that appear to be significantly worsened by oxidative stress. The effects of vitamin E on excitoxicity in cultured neurones is considered, together with ataxia due to vitamin E deficiency (AVED) arising from abetalipoproteinaemia, cholestatic liver disease, cystic fibrosis, short bowel syndrome, total parenteral nutrition, diabetic peripheral neuropathy and familial isolated vitamin E (FIVE) deficiency. Selenium deficiency in Keshan disease is also described in relation to the cardiomyopathy seen in
Friedreich's ataxia
. Evidence for any beneficial effects of vitamin E upon the course of
Friedreich's ataxia
, tardive dyskinesia, amyotrophic lateral sclerosis (motor neurone disease), Parkinson's disease, Alzheimer's disease, and Huntington's disease is examined. The application of vitamin E derivatives as protective agents in posttraumatic injury to the nervous system (stroke, head and spinal cord injury and haemorrhage) is discussed.
...
PMID:Vitamin E Status and Neurodegenerative Disease. 2740 31
Friedreich's Ataxia
(
FRDA
) is a neurodegenerative disorder, characterized by degeneration of dorsal root ganglia, cerebellum and cardiomyopathy. Heart failure is one of the most common causes of death for
FRDA
patients. Deficiency of frataxin, a small mitochondrial protein, is responsible for all clinical and morphological manifestations of
FRDA
. The focus of our study was to investigate the unexplored Ca
2+
homeostasis in cerebellar granule neurons (CGNs) and in cardiomyocytes of
FRDA
cellular models to understand the pathogenesis of degeneration. Ca
2+
homeostasis in neurons and cardiomyocytes is not only crucial for the cellular wellbeing but more importantly to generate action potential in both neurons and cardiomyocytes. By challenging Ca
2+
homeostasis in CGNs, and in adult and neonatal cardiomyocytes of
FRDA
models, we have assessed the impact of frataxin decrease on both neuronal and cardiac physiopathology. Interestingly, we have found that Ca
2+
homeostasis is altered both cell types. CGNs showed a Ca
2+
mishandling under depolarizing conditions and this was also reflected in the endoplasmic reticulum (ER) content. In cardiomyocytes we found that the sarcoplasmic reticulum (SR) Ca
2+
content was pathologically reduced, and that mitochondrial Ca
2+
uptake was impaired. This phenomenon is due to the excess of oxidative stress under
FRDA
like conditions and the consequent aberrant modulation of key players at the SR/ER and mitochondrial level that usually restore the Ca
2+
homeostasis. Our findings demonstrate that in both neurons and cardiomyocytes the decreased Ca
2+
level within the stores has a comparable detrimental impact in their physiology. In cardiomyocytes, we found that ryanodine receptors (RyRs) may be leaking and expel more Ca
2+
out from the SR. At the same time mitochondrial uptake was altered and we found that
Vitamin E
can restore this defect. Moreover,
Vitamin E
protects from cell death induced by hypoxia-reperfusion injury, revealing novel properties of
Vitamin E
as potential therapeutic tool for
FRDA
cardiomyopathy.
...
PMID:Calcium Deregulation: Novel Insights to Understand Friedreich's Ataxia Pathophysiology. 3033 28
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