Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0241981 (loss of balance)
 452 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A completely new mutational event associated with human diseases - the dynamic mutation - was discovered in the last decade. The molecular mechanism underlying dynamic mutation involves the expansion and intergenerational instability of a tandem-arrayed nucleotide sequence that acquire a pathological size, despite its polymorphic occurrence in normal individuals. To date, at least fourteen neurological disorders are associated with this phenomenon, including Huntington's disease (HD), dentatorubral and palidoluysian atrophy (DRPLA), spinobulbar and muscular atrophy (SBMA), myotonic dystrophy (DM), fragile X syndrome, FRAXE mental retardation and spinocerebellar ataxias (SCA) types 1-3, 6-8, 12 and 17. The spinocerebellar ataxias comprise a heterogeneous group of severe neurodegenerative-late onset disorders characterized by loss of balance and coordination. Most of the spinocerebellar ataxias exhibit an autosomal dominant pattern of inheritance and are promoted by the intergenerational expansion of a trinucleotide repeat (CAG)n inside the coding region of the respective gene. The expanded segment is translated into an abnormal polyglutamine tract in the protein, leading to the formation of nuclear aggregates that have been considered the basis of the pathogenesis in most of SCA types. One striking characteristic of these diseases is that the gene is expressed throughout the brain and also in other tissues but no pathological consequences are observed, despite the specific cellular degeneration. The characterization of the mutational event has led to the development of specific and sensitive molecular tests for direct DNA analysis, which allow confirmation of clinical diagnostic and an adequate therapeutic indication as well as genetic counseling.
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PMID:Dynamic mutation and human disorders: the spinocerebellar ataxias (review). 1471 38

Cancer cachexia is a highly debilitating paraneoplastic disease observed in more than 50% of patients with advanced cancers and directly contributes to 20% of cancer deaths. Skeletal muscle wasting is a prominent feature of the disease and is believed to result from the loss of balance between protein synthesis and degradation. Quality of life and prognosis are severely compromised in patients with cancer cachexia. Despite current knowledge on the mediators involved in cancer cachexia, treatment targeting a single molecule has rendered limited effectiveness. This article aims to review the mediators of cancer cachexia and interventions attempted in the literature and discuss the common pathways leading to protein loss that these mediators modulate during cachexia. We believe that by targeting downstream effectors that are common in these pathways, a better therapeutic approach to reverse muscle wasting and maintain muscle function during cancer cachexia will be achieved.
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PMID:Cancer cachexia: molecular targets and pathways for diagnosis and drug intervention. 2238 13