Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50502 (Hip)
 7,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a novel autosomal dominant myopathy presenting in mid-adult life with tibialis anterior weakness. We carried out a detailed clinical assessment of 24 individuals spanning three generations, documenting pathologic features of the muscles in 7 of the 11 affected individuals, including an autopsy study on one case. The second generation of affected individuals presented at an earlier age, and the disease progressed more rapidly than in the first generation. Lung function tests revealed progressive global respiratory muscle weakness detectable from the time of presentation, with preferential diaphragmatic involvement in some cases. Hip girdle and shoulder girdle weakness appeared later in the disease course. We observed a striking correlation between the clinical and pathological features. Clinically unaffected muscles had minimal pathologic change. Fiber splitting, eosinophilic inclusions, and vacuoles with basophilic rims were seen in moderately affected muscles, and fat and fibrous connective tissue replaced muscle fibers in the severely involved muscles. The inclusions were Congophilic and reacted with antibodies to desmin, beta-amyloid, and phosphorylated tau protein. The disease was not linked to any of the known loci associated with distal myopathies, confirming that the disorder in this family is both genetically and phenotypically distinct.
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PMID:A novel autosomal dominant distal myopathy with early respiratory failure: clinico-pathologic characteristics and exclusion of linkage to candidate genetic loci. 1131 Jun 21

Tauopathy is a pathological condition with an abnormal intracellular accumulation of tau protein in neurons and glias, which is a feature of Alzheimer's disease (AD) as well as frontotemporal lobar degenerations (FTLD). Recent reports showed that tauopathy occupies an important position for pathological process of dementia generally. Previously, we reported that endoplasmic reticulum (ER) stress has an influence on the onset of AD. In addition, some reports on brain autopsy findings suggest that ER stress is associated with AD and tauopathy. However, the mechanism underlying the association between ER stress and tauopathy is still unknown. Here, we show that ER stress, induced by glucose deprivation or chemicals, increases total endogenous tau protein in cultured neurons and primary cultured neurons. Under ER stress, no significant differences were observed in the transcription of tau, and no differences were observed in the translation of tau with or without the 5'-untranslated region (5'UTR) of tau. In contrast, the degradation rate of tau was decreased by 20% under ER stress. ER stress reduced the binding between tau and carboxyl terminus of Hsc70-interacting protein (CHIP), ubiquitin E3 ligase for tau. These results suggest that ER stress increases total tau protein and its mechanism is due to the decrease in the binding between tau and CHIP, which delays the degradation of tau protein through the ubiquitin-proteasome pathway. This mechanism may provide clue to treatment for tauopathy.
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PMID:Involvement of endoplasmic reticulum stress in tauopathy. 2323 6