{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T16:28:09Z","timestamp":1770913689590,"version":"3.50.1"},"reference-count":48,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2011,6,10]],"date-time":"2011-06-10T00:00:00Z","timestamp":1307664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human T\u2010cell leukemia virus type I (HTLV\u2010I)\u2010associated myelopathy\/tropical spastic paraparesis (HAM\/TSP) is a neurodegenerative disease characterized by selective loss of axons and myelin in the corticospinal tracts. This central axonopathy may originate from the impairment of anterograde axoplasmic transport. Previous work showed tau hyperphosphorylation at T<jats:sup>181<\/jats:sup> in cerebrospinal fluid of HAM\/TSP patients. Similar hyperphosphorylation occurs in SH\u2010SY5Y cells incubated with supernatant from MT\u20102 cells (HTLV\u2010I\u2010infected lymphocytes secreting viral proteins, including Tax) that produce neurite shortening. Tau phosphorylation at T<jats:sup>181<\/jats:sup> is attributable to glycogen synthase kinase 3\u2010\u03b2 (GSK3\u2010\u03b2) and cyclin\u2010dependent kinase 5 (CDK5) activation. Here we investigate whether neurite retraction in the SH\u2010SY5Y model associates with concurrent changes in other tau hyperphosphorylable residues. Threonine 181 turned out to be the only tau hyperphosphorylated residue. We also evaluate the role of GSK3\u2010\u03b2 and CDK5 in this process by using specific kinase inhibitors (LiCl, TDZD\u20108, and roscovitine). Changes in both GSK3\u2010\u03b2 active and inactive forms were followed by measuring the regulatory phosphorylable sites (S<jats:sup>9<\/jats:sup> and Y<jats:sup>216<\/jats:sup>, inactivating and activating phosphorylation, respectively) together with changes in \u03b2\u2010catenin protein levels. Our results showed that LiCl and TDZD\u20108 were unable to prevent MT\u20102 supernatant\u2010mediated neurite retraction and also that neither Y<jats:sup>216<\/jats:sup> nor S<jats:sup>9<\/jats:sup> phosphorylations were changed in GSK3\u2010\u03b2. Thus, GSK3\u2010\u03b2 seems not to play a role in T<jats:sup>181<\/jats:sup> hyperphosphorylation. On the other hand, the CDK5 involvement in tau phosphorylation was confirmed by both the increase in its enzymatic activity and the absence of MT\u20102 neurite retraction in the presence of roscovitine or CDK5 siRNA transfection. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.22678","type":"journal-article","created":{"date-parts":[[2011,6,10]],"date-time":"2011-06-10T17:29:03Z","timestamp":1307726943000},"page":"1489-1498","source":"Crossref","is-referenced-by-count":24,"title":["Inhibition of cyclin\u2010dependent kinase 5 but not of glycogen synthase kinase 3\u2010\u03b2 prevents neurite retraction and tau hyperphosphorylation caused by secretable products of human T\u2010cell leukemia virus type I\u2010infected 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