Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0016719 (Friedreich's ataxia)
 2,098 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Friedreich's Ataxia (FA) is an inherited neurodegenerative disorder resulting from decreased expression of the mitochondrial protein frataxin, for which there is no approved therapy. High throughput screening of clinically used drugs identified Dimethyl fumarate (DMF) as protective in FA patient cells. Here we demonstrate that DMF significantly increases frataxin gene (FXN) expression in FA cell model, FA mouse model and in DMF treated humans. DMF also rescues mitochondrial biogenesis deficiency in FA-patient derived cell model. We further examined the mechanism of DMF's frataxin induction in FA patient cells. It has been shown that transcription-inhibitory R-loops form at GAA expansion mutations, thus decreasing FXN expression. In FA patient cells, we demonstrate that DMF significantly increases transcription initiation. As a potential consequence, we observe significant reduction in both R-loop formation and transcriptional pausing thereby significantly increasing FXN expression. Lastly, DMF dosed Multiple Sclerosis (MS) patients showed significant increase in FXN expression by ~85%. Since inherited deficiency in FXN is the primary cause of FA, and DMF is demonstrated to increase FXN expression in humans, DMF could be considered for Friedreich's therapy.
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PMID:Dimethyl fumarate dosing in humans increases frataxin expression: A potential therapy for Friedreich's Ataxia. 3115 68

Iron has been proposed to be responsible for neuronal loss in several diseases of the central nervous system, including Alzheimer's disease (AD), Parkinson's disease (PD), stroke, Friedreich's ataxia (FRDA), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS). In many diseases, abnormal accumulation of brain iron in disease-affected area has been observed, without clear knowledge of the contribution of iron overload to pathogenesis. Recent evidences implicate that key proteins involved in the disease pathogenesis may also participate in cellular iron metabolism, suggesting that the imbalance of brain iron homeostasis is associated with the diseases. Considering the complicated regulation of iron homeostasis within the brain, a thorough understanding of the molecular events leading to this phenotype is still to be investigated. However, current understanding has already provided the basis for the diagnosis and treatment of iron-related CNS diseases, which will be reviewed here.
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PMID:Diagnostics and Treatments of Iron-Related CNS Diseases. 3145 11

Neurodegenerative diseases (NDs) cause progressive loss of neurons in nervous system. NDs are categorized as acute NDs such as stroke and head injury, besides chronic NDs including Alzheimer's, Parkinson's, Huntington's diseases, Friedreich's Ataxia, Multiple Sclerosis. The exact etiology of NDs is not understood but oxidative stress, inflammation and synaptic dysfunction are main hallmarks. Oxidative stress leads to free radical attack on neural cells which contributes to protein misfolding, glia cell activation, mitochondrial dysfunction, impairment of DNA repair system and subsequently cellular death. Neural stem cells (NSCs) support adult neurogenesis in nervous system during injuries which is limited to certain regions in brain. NSCs can differentiate into the neurons, astrocytes or oligodendrocytes. Impaired neurogenesis and inadequate induction of neurogenesis are the main obstacles in treatment of NDs. Protection of neural cells from oxidative damages and supporting neurogenesis are promising strategies to treat NDs. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a transcriptional master regulator that maintains the redox homeostasis in cells by provoking expression of antioxidant, anti-inflammatory and cytoprotective genes. Nrf2 can strongly influence the NSCs function and fate determination by reducing levels of reactive oxygen species in benefit of NSC survival and neurogenesis. In this review we will summarize the role of Nrf2 in NSC function, and exogenous and endogenous therapeutic strategies in treatment of NDs.
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PMID:The role of Nrf2 in neural stem/progenitors cells: From maintaining stemness and self-renewal to promoting differentiation capability and facilitating therapeutic application in neurodegenerative disease. 3318 70

The postural control assessments in patients with neurological diseases lack reliability and sensitivity to small changes in patient functionality. The appearance of pressure mapping has allowed quantitative evaluation of postural control in sitting. This study was carried out to determine the evaluations in pressure mapping and verifying whether they are different between the three sample groups (multiple sclerosis, spinal cord injury and Friedreich's ataxia), and to determine whether the variables extracted from the pressure mapping analysis are more sensitive than functional tests to evaluate the postural trunk control. A case series study was carried out in a sample of 10 adult patients with multiple sclerosis (n = 2), spinal cord injury (n = 4) and Friedreich's ataxia (n = 4). The tests applied were: pressure mapping, seated Lateral Reach Test, seated Functional Reach Test, Berg Balance Scale, Posture and Postural Ability Scale, Function in Sitting Test, and Trunk Control Test. The participants with Friedreich's ataxia showed a tendency to present a higher mean pressure on the seat of subject's wheelchair compared to other groups. In parallel, users with spinal cord injury showed a tendency to present the highest values of maximum pressure and area of contact. People with different neurological pathologies and similar results in functional tests have very different results in the pressure mapping. Although it is not possible to establish a strong statistical correlation, the relationships between the pressure mapping variables and the functional tests seem to be numerous, especially in the multiple sclerosis group.
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PMID:Analysis of Postural Control in Sitting by Pressure Mapping in Patients with Multiple Sclerosis, Spinal Cord Injury and Friedreich's Ataxia: A Case Series Study. 3320 27


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