Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spinocerebellar ataxia type 17 (SCA17) is caused by CAG/CAA repeat expansion on the gene encoding a general transcription factor, TATA-box-binding protein (TBP). The CAG repeat expansion leads to the reduced solubility of polyglutamine TBP and induces aggregate formation. The TBP aggregation, mostly present in the cell nuclei, is distinct from that in most other neurodegenerative diseases, in which the aggregation is formed in cytosol or extracellular compartments. Trehalose is a disaccharide issued by the Food and Drug Administration with a Generally Recognized As Safe status. Lines of evidence suggest trehalose could prevent protein aggregate formation in several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. In this study, we evaluated the therapeutic potential of trehalose on SCA17 using cerebellar primary and organotypic culture systems and a mouse model. Our results showed that TBP nuclear aggregation was significantly decreased in both the primary and slice cultures. Trehalose (4 %) was further supplied in the drinking water of SCA17 transgenic mice. We found both the gait behavior in the footprint analysis and motor coordination in the rotarod task were significantly improved in the trehalose-treated SCA17 mice. The cerebellar weight was increased and the astrocyte gliosis was reduced in SCA17 mice after trehalose treatment. These data suggest that trehalose could be a potential nontoxic treatment for SCA17.
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PMID:Trehalose attenuates the gait ataxia and gliosis of spinocerebellar ataxia type 17 mice. 2567 22

Autophagy impairment has been demonstrated in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) and could be a new target of treatment. Trehalose is a natural, nonreducing disaccharide that has been shown to enhance autophagy. Therefore, we investigated whether trehalose treatment reduces renal cyst formation in a Pkd1-hypomorphic mouse model. Pkd1 miRNA transgenic (Pkd1 miR Tg) mice and wild-type littermates were given drinking water supplemented with 2% trehalose from postnatal day 35 to postnatal day 91. The control groups received pure water or 2% sucrose for the control of hyperosmolarity. The effect on kidney weights, cystic indices, renal function, cell proliferation, and autophagic activities was determined. We found that Pkd1 miR Tg mice had a significantly lower renal mRNA expression of autophagy-related genes, including atg5, atg12, ulk1, beclin1, and p62, compared with wild-type control mice. Furthermore, immunohistochemical analysis showed that cystic lining cells had strong positive staining for the p62 protein, indicating impaired degradation of the protein by the autophagy-lysosome pathway. However, trehalose treatment did not improve reduced autophagy activities, nor did it reduce relative kidney weights, plasma blood urea nitrogen levels, or cystatin C levels in Pkd1 miR Tg mice. Histomorphological analysis revealed no significant differences in the renal cyst index, fibrosis score, or proliferative score among trehalose-, sucrose-, and water-treated groups. Our results demonstrate that adding trehalose to drinking water does not modulate autophagy activities and renal cystogenesis in Pkd1-deficient mice, suggesting that an oral supplement of trehalose may not affect the progression of ADPKD.
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PMID:Effect of Trehalose Supplementation on Autophagy and Cystogenesis in a Mouse Model of Polycystic Kidney Disease. 3058 17