Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brain insulin-like growth factor I (IGF-I) and its related molecules may be involved in neurodegenerative processes in which IGF-I-containing pathways are compromised. Since IGF-I is present in the olivocerebellar circuitry, two types of late-onset cerebellar ataxias (olivopontocerebellar and idiopathic cerebellar cortical atrophy) were chosen to test this hypothesis. The following significant changes in the peripheral IGF-I system of these patients were found: low IGF-I levels, and high IGF-binding protein 1 (BP-1), and BP-3 affinity for IGF-1. Sixty percent of the patients also had significantly low insulin levels. Patients suffering from other neurological diseases with cerebellar dysfunction and ataxia not involving the olivocerebellar pathway also had low IGF-I levels, while IGFBPs and insulin levels were normal. Our data indicate that degeneration of an IGF-I-containing neuronal pathway produces significant changes in the peripheral IGF system. This suggests strongly that the endocrine (bloodborne) and the paracrine/autocrine (brain) IGF systems are linked functionally. We propose that alterations in the blood IGF-I system may constitute a marker of some cerebellar diseases.
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PMID:The insulin-like growth factor I system in cerebellar degeneration. 860 52

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by progressive ataxia, elevated cancer incidence, and premature aging. A-T cells, Atm-deficient mice, and individuals with A-T show increased oxidant sensitivity, genomic instability, altered IGF-1 and p53 signaling, and rapid telomere shortening compared to normal controls. The gene mutated in A-T, ATM, regulates DNA repair, IGF-1 and p53 signaling, age pigment removal, antioxidant capacity, and telomere maintenance - pathways involved in and often attenuated with aging. Interestingly, flavonoids with chemopreventative effects, such as quercetin, genistein, and epigallocatechin gallate activate ATM. Since ATM activates pathways which increase genomic stability, oxidant resistance, and/or telomere stability, and since many diseases of old age (i.e., cancer, cardiovascular and neurodegenerative disease), result from attenuation of these pathways, pharmacologic manipulation of ATM activity via flavonoid intake may prove useful in slowing the appearance of age-associated disease.
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PMID:Pharmacologic manipulation of the ataxia-telangiectasia mutated gene product as an intervention in age-related disease. 1592 13

Rett syndrome (RTT) is an autism spectrum disorder mainly caused by mutations in the X-linked MECP2 gene and affecting roughly 1 out of 10.000 born girls. Symptoms range in severity and include stereotypical movement, lack of spoken language, seizures, ataxia and severe intellectual disability. Notably, muscle tone is generally abnormal in RTT girls and women and the Mecp2-null mouse model constitutively reflects this disease feature. We hypothesized that MeCP2 in muscle might physiologically contribute to its development and/or homeostasis, and conversely its defects in RTT might alter the tissue integrity or function. We show here that a disorganized architecture, with hypotrophic fibres and tissue fibrosis, characterizes skeletal muscles retrieved from Mecp2-null mice. Alterations of the IGF-1/Akt/mTOR pathway accompany the muscle phenotype. A conditional mouse model selectively depleted of Mecp2 in skeletal muscles is characterized by healthy muscles that are morphologically and molecularly indistinguishable from those of wild-type mice raising the possibility that hypotonia in RTT is mainly, if not exclusively, mediated by non-cell autonomous effects. Our results suggest that defects in paracrine/endocrine signaling and, in particular, in the GH/IGF axis appear as the major cause of the observed muscular defects. Remarkably, this is the first study describing the selective deletion of Mecp2 outside the brain. Similar future studies will permit to unambiguously define the direct impact of MeCP2 on tissue dysfunctions.
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PMID:MeCP2 Affects Skeletal Muscle Growth and Morphology through Non Cell-Autonomous Mechanisms. 2609 33