Artículos de revistas
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
Fecha
2011Registro en:
Journal of Neuroscience Research, Volumen 89, Issue 9, 2018, Pages 1489-1498
03604012
10974547
10.1002/jnr.22678
Autor
Maldonado, Horacio
Ramírez, Eugenio
Utreras Puratich, Elías
Pando, María E.
Kettlun, Ana M.
Chiong Lay, Mario
Kulkarni, Ashok B.
Collados, Lucía
Puente, Javier
Cartier Rovirosa, Luis
Valenzuela, María A.
Institución
Resumen
Human 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 T 181 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 T 181 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