C. Atzori et al., Activation of the JNK/p38 pathway occurs in diseases characterized by tau protein pathology and is related to tau phosphorylation but not to apoptosis, J NE EXP NE, 60(12), 2001, pp. 1190-1197
Citations number
40
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
JNK and p38, two members of the MAP kinase family, are strongly induced by
various stresses including oxidative stress and have been involved in regul
ation of apoptosis. As both kinases phosphorylate tau protein in vitro, we
have investigated their immunohistochemical localization in a group of neur
odegenerative diseases characterized by intracellular deposits of hyperphos
phorylated tau, Cases included Alzheimer disease, Pick disease, progressive
supranuclear palsy, corticobasal degeneration, Gerstmann-Straussler-Schein
ker disease-Indiana kindred, and frontotemporal dementia with parkinsonism
linked to chromosome 17. In all tissue samples, strong immunoreactivity for
both MAP kinases was found in the same neuronal or glial cells that contai
ned tau-positive deposits. By double immunohistochemistry, JNK and p38 colo
calized with tau in the inclusions. Analysis of apoptosis-related changes (
DNA fragmentation, activated caspase-3) showed that the expression of JNK a
nd p38 was unrelated to activation of an apoptotic cascade. Our data indica
te that phospho-JNK and phospho-p38 are associated with hyperphosphorylated
tau in a variety of abnormal tau inclusions, suggesting that these kinases
may play a role in the development of degenerative diseases with tau patho
logy.