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)

The erythroid-specific (ALAS2) and housekeeping (ALAS1) genes encoding delta-aminolevulinate synthase have recently been mapped to chromosomes Xp21.1----q21 and 3p21, respectively. The erythroid-specific gene is a candidate for mutations resulting in X-linked sideroblastic anemia. Analysis of DNA from hybrid clones containing translocations in the region Xp11.21----Xq21.3 permitted the finer localization of the ALAS2 gene with respect to other loci and breakpoints within this region. These studies localized the ALAS2 gene to the distal subregion of Xp11.21 in Interval 5 indicating the following gene order: Xpter-OATL2-[L62-3A, Xp11.21; A62-1A-4b, Xp11.21]-(ALAS2, DXS323)-[B13-3, Xp11.21; C9-5, Xp11.21]-(DXS14, DXS429)-DXS422-(DXZ1, Xcen). Thus, the reported linkage of acquired sideroblastic anemia and sideroblastic anemia with ataxia to Xq13 presumably results from genes other than ALAS2.
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PMID:Assignment of human erythroid delta-aminolevulinate synthase (ALAS2) to a distal subregion of band Xp11.21 by PCR analysis of somatic cell hybrids containing X; autosome translocations. 157 84

Plasma membrane Ca(2+)-ATPases (PMCAs) are high-affinity calcium pumps that contribute to the maintenance of intracellular Ca(2+) homeostasis by exporting Ca(2+) from the cytosol to the extracellular environment. Mammals have four genes encoding the proteins PMCA1 through PMCA4. Each gene transcript is alternatively spliced to generate several variants. Their distribution is tissue- and cell-specific and undergoes regulation during cell development and differentiation. Traditionally, these pumps have been considered to play a housekeeping role in controlling basal Ca(2+) levels, but more recently, it became clear that the presence (and the co-expression) of different isoforms must be related to a more specialized function. Only one of the four genes (encoding PMCA2) has been causally linked to disease in mammals: Several spontaneous mutations are responsible for deafness and ataxia. Other complex human disease phenotype like hearing loss, cardiac function, and infertility are likely to be associated with PMCA function, but no spontaneous mutations in other PMCA genes than PMCA2 are so far identified. The evidence of their involvement in disease phenotypes comes from studies on isoform-specific knockout mice. In this review, I will discuss briefly the general role of PMCA as essential component of Ca(2+) homeostasis machinery and focus on its emerging role as signaling molecule with particular attention on the diseases caused by PMCA dysfunction.
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PMID:Plasma membrane Ca(2+)-ATPase: from a housekeeping function to a versatile signaling role. 1854 70

The Ca(2+) ATPases of the plasma membrane (PMCA pumps) export Ca(2+) from all eukaryotic cells. In mammals they are the products of four separate genes. PMCA types 1 and 4 are distributed ubiquitously; PMCA types 2 and 3 are restricted to some tissues, the most important being the nervous system. Alternative splicing at two sites greatly increases the number of pump isoforms. The two ubiquitous isoforms are no longer considered as only housekeeping pumps as they also perform tissue-specific functions. The PMCAs are classical P-type pumps, their reaction cycle repeating that of all other pumps of the family. Their 3D structure has not been solved, but molecular modeling on SERCA pump templates shows the essential structural pattern of the latter. PMCAs are regulated by calmodulin, which interacts with high affinity with their cytosolic C-terminal tail. A second calmodulin-binding domain with lower affinity is present in some splicing variants of the pump. The PMCAs are essential to the regulation of cellular Ca(2+), but the all-important Ca(2+) signal is ambivalent: defects in its control generate various pathologies, the most thoroughly studied being those of genetic origin. Genetic defects of PMCA function produce disease phenotypes: the best characterized is a form of deafness in mice and in humans linked to PMCA2 mutations. A cerebellar X-linked human ataxia has recently been found to be caused by a mutation in the calmodulin-binding domain of PMCA3.
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PMID:The plasma membrane calcium pump in health and disease. 2341 90

Autophagy ensures the lysosome-mediated breakdown and recycling of self-material, as it not only degrades obsolete or damaged intracellular constituents but also provides building blocks for biosynthetic and energy producing reactions. Studies in animal models including Drosophila revealed that autophagy defects lead to the rapid decline of neuromuscular function, neurodegeneration, sensitivity to stress (such as starvation or oxidative damage), and stem cell loss. Of note, recently identified human Atg gene mutations cause similar symptoms including ataxia and mental retardation. Physiologically, autophagic degradation (flux) is known to decrease during aging, and this defect likely contributes to the development of such age-associated diseases. Many manipulations that extend lifespan (including dietary restriction, reduced TOR kinase signaling, exercise or treatment with various anti-aging substances) require autophagy for their beneficial effect on longevity, pointing to the key role of this housekeeping process. Importantly, genetic (e.g., Atg8a overexpression in either neurons or muscle) or pharmacological (e.g., feeding rapamycin or spermidine to animals) promotion of autophagy has been successfully used to extend lifespan in Drosophila, suggesting that this intracellular degradation pathway can rejuvenate cells and organisms. In this review, we highlight key discoveries and recent progress in understanding the relationship of autophagy and aging in Drosophila.
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PMID:On the Fly: Recent Progress on Autophagy and Aging in Drosophila. 3139 11