DOI: 10.1002/jnr.22678. Inhibition of cyclin‐dependent kinase 5 but not of glycogen synthase kinase 3‐β prevents neurite retraction and tau hyperphosphorylation caused by secretable products of human T‐cell leukemia virus type I‐infected lymphocytes

Inhibition of cyclin‐dependent kinase 5 but not of glycogen synthase kinase 3‐β prevents neurite retraction and tau hyperphosphorylation caused by secretable products of human T‐cell leukemia virus type I‐infected lymphocytes

10.1002/jnr.22678

Crossref journal-article

Wiley

Journal of Neuroscience Research (311)

Abstract

AbstractHuman T‐cell leukemia virus type I (HTLV‐I)‐associated 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 T181 in cerebrospinal fluid of HAM/TSP patients. Similar hyperphosphorylation occurs in SH‐SY5Y cells incubated with supernatant from MT‐2 cells (HTLV‐I‐infected lymphocytes secreting viral proteins, including Tax) that produce neurite shortening. Tau phosphorylation at T181 is attributable to glycogen synthase kinase 3‐β (GSK3‐β) and cyclin‐dependent kinase 5 (CDK5) activation. Here we investigate whether neurite retraction in the SH‐SY5Y 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‐β and CDK5 in this process by using specific kinase inhibitors (LiCl, TDZD‐8, and roscovitine). Changes in both GSK3‐β active and inactive forms were followed by measuring the regulatory phosphorylable sites (S9 and Y216, inactivating and activating phosphorylation, respectively) together with changes in β‐catenin protein levels. Our results showed that LiCl and TDZD‐8 were unable to prevent MT‐2 supernatant‐mediated neurite retraction and also that neither Y216 nor S9 phosphorylations were changed in GSK3‐β. Thus, GSK3‐β seems not to play a role in T181 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‐2 neurite retraction in the presence of roscovitine or CDK5 siRNA transfection. © 2011 Wiley‐Liss, Inc.

Bibliography

Maldonado, H., RamÃrez, E., Utreras, E., Pando, M. E., Kettlun, A. M., Chiong, M., Kulkarni, A. B., Collados, L., Puente, J., Cartier, L., & Valenzuela, M. A. (2011). Inhibition of cyclinâdependent kinase 5 but not of glycogen synthase kinase 3âÎ² prevents neurite retraction and tau hyperphosphorylation caused by secretable products of human Tâcell leukemia virus type Iâinfected lymphocytes. Journal of Neuroscience Research, 89(9), 1489â1498. Portico.

Authors 11

Horacio Maldonado (first)
Eugenio Ramírez (additional)
Elias Utreras (additional)
María E. Pando (additional)
Ana M. Kettlun (additional)
Mario Chiong (additional)
Ashok B. Kulkarni (additional)
Lucía Collados (additional)
Javier Puente (additional)
Luis Cartier (additional)
María A. Valenzuela (additional)

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Dates

Type	When
Created	14 years, 2 months ago (June 10, 2011, 1:29 p.m.)
Deposited	1 year, 10 months ago (Oct. 16, 2023, 2:35 a.m.)
Indexed	1 month, 1 week ago (July 24, 2025, 7:41 a.m.)
Issued	14 years, 2 months ago (June 10, 2011)
Published	14 years, 2 months ago (June 10, 2011)
Published Online	14 years, 2 months ago (June 10, 2011)
Published Print	14 years ago (Sept. 1, 2011)

Funders 0

None

BibTeX

@article{Maldonado_2011, title={Inhibition of cyclin‐dependent kinase 5 but not of glycogen synthase kinase 3‐β prevents neurite retraction and tau hyperphosphorylation caused by secretable products of human T‐cell leukemia virus type I‐infected lymphocytes}, volume={89}, ISSN={1097-4547}, url={http://dx.doi.org/10.1002/jnr.22678}, DOI={10.1002/jnr.22678}, number={9}, journal={Journal of Neuroscience Research}, publisher={Wiley}, author={Maldonado, Horacio and Ramírez, Eugenio and Utreras, Elias and Pando, María E. and Kettlun, Ana M. and Chiong, Mario and Kulkarni, Ashok B. and Collados, Lucía and Puente, Javier and Cartier, Luis and Valenzuela, María A.}, year={2011}, month=jun, pages={1489–1498} }

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