http://rdf.ncbi.nlm.nih.gov/pubchem/patent/US-9599626-B2

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filingDate 2012-11-29-04:00^^<http://www.w3.org/2001/XMLSchema#date>
grantDate 2017-03-21-04:00^^<http://www.w3.org/2001/XMLSchema#date>
inventor http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_d4ceae4c31c053bfdb606ab43b952a96
publicationDate 2017-03-21-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber US-9599626-B2
titleOfInvention Therapeutic and diagnostic method for ataxia-telangiectasia
abstract ATM kinase is shown to regulate proteasome-mediated protein turnover through suppression of the expression of the ubiquitin-like protein ISG15 (Interferon Stimulated Gene 15). Silencing of the ISG15 pathway restored both the ubiquitin and autophagy pathways, and the UV-mediated degradation of their substrates in A-T cells. The ATM kinase negatively regulates the ISG15 pathway, and the constitutively elevated ISG15 pathway induces proteinopathy in A-T cells, and in A-T patients. These findings indicate that proteasome-mediated protein degradation is impaired in A-T cells due to elevated expression of the ISG15 conjugation pathway, which contributes to progressive neurodegeneration in A-T patients. The ISG15 pathway is a new target for both detection and treatment of A-T Inhibitors if ISG15 expression can be used to inhibit or attenuate neurodegeneration in A-T patients. In addition, an inhibitor of the early phase of autophagy, 3-MA, was shown to be effective in decreasing the impaired proteasome-mediated protein degradation in A-T cells, and thus would be effective in decreasing the neurodegeneration in A-T patients.
priorityDate 2011-12-01-04:00^^<http://www.w3.org/2001/XMLSchema#date>
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