{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:54:19Z","timestamp":1781103259532,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1995,3,14]]},"abstract":"<jats:p>Brain pathology in Alzheimer disease and in aged controls shows hyperphosphorylation of tau and of neurofilament proteins. Roder and Ingram [Roder, H.M. &amp; Ingram, V.M. (1991) J. Neurosci. 11, 3325-3343 and Roder, H.M., Eden, P.A. &amp; Ingram, V.M. (1993) Biochem. Biophys. Res. Commun. 193, 639-647] previously reported that the brain protein kinase PK40erk can hyperphosphorylate both tau and neurofilaments and interestingly, is strongly inhibited by ATP uncomplexed with Mg2+. We now report that the mitochondrial uncoupler carbonyl cyanide p-trifluoro-methoxyphenylhydrazone decreases ATP levels in rat pheochromacytoma (PC-12) cells differentiated with nerve growth factor and activates a neurofilament kinase, a tau kinase, and, unexpectedly, a tau phosphatase--either PP1 or PP2A. Such aberrant modulation of protein phosphorylation patterns could be the common biochemical basis for senile dementia and for Alzheimer disease and could explain the late-onset etiology of both conditions.<\/jats:p>","DOI":"10.1073\/pnas.92.6.1861","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T09:29:22Z","timestamp":1149067762000},"page":"1861-1865","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":24,"title":["Activation of a neurofilament kinase, a tau kinase, and a tau phosphatase by decreased ATP levels in nerve growth factor-differentiated PC-12 cells."],"prefix":"10.1073","volume":"92","author":[{"given":"M L","family":"Bush","sequence":"first","affiliation":[{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge 02139."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J S","family":"Miyashiro","sequence":"additional","affiliation":[{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge 02139."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V M","family":"Ingram","sequence":"additional","affiliation":[{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge 02139."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1995,3,14]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.92.6.1861","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T14:05:57Z","timestamp":1649858757000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.92.6.1861"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,3,14]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1995,3,14]]}},"alternative-id":["10.1073\/pnas.92.6.1861"],"URL":"https:\/\/doi.org\/10.1073\/pnas.92.6.1861","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,3,14]]},"assertion":[{"value":"1995-03-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}