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Belfer Family Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010302","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    The discovery of the causative gene for Huntington\u2019s disease (HD) has promoted numerous efforts to uncover cellular pathways that lower levels of mutant huntingtin protein (mHtt) and potentially forestall the appearance of HD-related neurological defects. Using a cell-based model of pathogenic huntingtin expression, we identified a class of compounds that protect cells through selective inhibition of a lipid kinase, PIP4K\u03b3. Pharmacological inhibition or knock-down of PIP4K\u03b3 modulates the equilibrium between phosphatidylinositide (PI) species within the cell and increases basal autophagy, reducing the total amount of mHtt protein in human patient fibroblasts and aggregates in neurons. In two\n                    <jats:italic>Drosophila<\/jats:italic>\n                    models of Huntington\u2019s disease, genetic knockdown of PIP4K ameliorated neuronal dysfunction and degeneration as assessed using motor performance and retinal degeneration assays respectively. Together, these results suggest that PIP4K\u03b3 is a druggable target whose inhibition enhances productive autophagy and mHtt proteolysis, revealing a useful pharmacological point of intervention for the treatment of Huntington\u2019s disease, and potentially for other neurodegenerative disorders.\n                  <\/jats:p>","DOI":"10.7554\/elife.29123","type":"journal-article","created":{"date-parts":[[2017,12,19]],"date-time":"2017-12-19T08:00:29Z","timestamp":1513670429000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.29123","source":"Crossref","is-referenced-by-count":60,"title":["Inhibition of PIP4K\u03b3 ameliorates the pathological effects of mutant huntingtin protein"],"prefix":"10.7554","volume":"6","author":[{"given":"Ismael","family":"Al-Ramahi","sequence":"first","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States"},{"name":"Baylor College of Medicine, Texas Medical Center, Houston, United 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