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)

Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 is an autosomal dominant spinocerebellar degeneration characterized by a wide range of clinical manifestations. Unstable CAG trinucleotide repeat expansion in the MJD gene has been identified as the pathologic mutation of MJD. In this study, human SK-N-SH neuroblastoma cells stably transfected with full-length MJD with 78 CAG repeats were established. Compared with the parental cells, cells expressing mutant ataxin-3 displayed normal morphology for over 80 generations. Less than 1% of the transfected cells contained nuclear aggregates under basal conditions, indicating that this cellular model represented an early disease stage. While t-butyl hydroperoxide (TBH) was used to assess the oxidative tolerance of cells, the results demonstrated that the transfected cells were more susceptible to low concentrations of TBH than the parental cells. Most interestingly, from 2D gel electrophoresis analysis, we identified that the expression of heat shock protein 27 (HSP27), known as a suppressor of poly(Q)-mediated cell death, dramatically decreased in SK-N-SH cells stably transfected with full-length mutant MJD. The same reduction of HSP27 was further confirmed in lymphoblastoid cells from MJD patients. Our results demonstrated that both neuronal and non-neuronal cells with expanded full-length ataxin-3 revealed reduced protein expression of HSP27. We propose that the reduction of HSP27 in the early stage of the disease plays an important role during cell death process in MJD.
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PMID:Down-regulation of heat shock protein 27 in neuronal cells and non-neuronal cells expressing mutant ataxin-3. 1283 59

Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant spinocerebellar degeneration characterized by a wide range of clinical manifestations. In this review, we discuss the role(s) that heat shock protein 27 (HSP27) may play in the cell death process of spinocerebellar ataxia type 3.
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PMID:HSP27 and cell death in spinocerebellar ataxia type 3. 1589 56

Spontaneous mutation in the lysosomal acid phosphatase 2 (Acp2) mouse (nax--naked-ataxia mutant mouse) correlates with severe cerebellar defects including ataxia, reduced size and abnormal lobulation as well as Purkinje cell (Pc) degeneration. Loss of Pcs in the nax cerebellum is compartmentalized and harmonized to the classic pattern of gene expression of the cerebellum in the wild type mouse. Usually, degeneration starts in the anterior and posterior zones and continues to the central and nodular zones of cerebellum. Studies have suggested that the p75 neurotrophin receptor (NTR) plays a role in Pc degeneration; thus, in this study, we investigated the p75NTR pattern and protein expression in the cerebellum of the nax mutant mouse. Despite massive Pc degeneration that was observed in the nax mouse cerebellum, p75NTR pattern expression was similar to the HSP25 pattern in nax mice and comparable with wild type sibling cerebellum. In addition, immunoblot analysis of p75NTR protein expression did not show any significant difference between nax and wild type sibling (p > 0.5). In comparison with wild type counterparts, p75NTR pattern expression is aligned with the fundamental cytoarchitecture organization of the cerebellum and is unchanged in the nax mouse cerebellum despite the severe neurodevelopmental disorder accompanied with Pc degeneration.
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PMID:Cerebellar Expression of the Neurotrophin Receptor p75 in Naked-Ataxia Mutant Mouse. 2678 82