Active stress kinase p38 enhances and perpetuates abnormal tau phosphorylation and deposition in Pick's disease
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Active stress kinase p38 enhances and perpetuates abnormal tau phosphorylation and deposition in Pick's disease. / Puig, Berta; Vinals, Francesc; Ferrer, Isidre; Puig Martorell, Berta.
In: ACTA NEUROPATHOL, Vol. 107, No. 3, 01.03.2004, p. 185-9.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Active stress kinase p38 enhances and perpetuates abnormal tau phosphorylation and deposition in Pick's disease
AU - Puig, Berta
AU - Vinals, Francesc
AU - Ferrer, Isidre
AU - Puig Martorell, Berta
PY - 2004/3/1
Y1 - 2004/3/1
N2 - Abnormal tau hyperphosphorylation and deposition in Pick bodies is a major abnormality in Pick's disease (PiD). This is associated with increased expression of the stress-activated protein kinase, p38 kinase, which has the capacity to phosphorylate tau in vitro. The present study has shown increased expression of phosphorylated p38 (p38-P), which does not cross-react with phospho-tau, in sarcosyl-insoluble fractions enriched in abnormal filaments, and hyperphosphorylated tau in the brain of two PiD cases obtained and processed with very short (less than 2 h) post-mortem delay. Immunohistochemical studies have shown p38-P co-localization in 90% of neurons with Pick bodies, whereas no positive cells are encountered in control brains processed in parallel. Moreover, p38-immunoprecipitated from sarcosyl-insoluble fractions in PiD brains is functionally active as it has the capacity to phosphorylate its specific substrate ATF-2. Combined biochemical, immunohistochemical and functional studies indicate that active p38 kinase is expressed in a very high percentage of Pick bodies, thus suggesting a critical role of this kinase in enhancing and perpetuating tau hyperphosphorylation in PiD.
AB - Abnormal tau hyperphosphorylation and deposition in Pick bodies is a major abnormality in Pick's disease (PiD). This is associated with increased expression of the stress-activated protein kinase, p38 kinase, which has the capacity to phosphorylate tau in vitro. The present study has shown increased expression of phosphorylated p38 (p38-P), which does not cross-react with phospho-tau, in sarcosyl-insoluble fractions enriched in abnormal filaments, and hyperphosphorylated tau in the brain of two PiD cases obtained and processed with very short (less than 2 h) post-mortem delay. Immunohistochemical studies have shown p38-P co-localization in 90% of neurons with Pick bodies, whereas no positive cells are encountered in control brains processed in parallel. Moreover, p38-immunoprecipitated from sarcosyl-insoluble fractions in PiD brains is functionally active as it has the capacity to phosphorylate its specific substrate ATF-2. Combined biochemical, immunohistochemical and functional studies indicate that active p38 kinase is expressed in a very high percentage of Pick bodies, thus suggesting a critical role of this kinase in enhancing and perpetuating tau hyperphosphorylation in PiD.
KW - Activating Transcription Factor 2
KW - Animals
KW - Blotting, Western
KW - Brain
KW - Case-Control Studies
KW - Cell Count
KW - Cell Fractionation
KW - Cell Line
KW - Cyclic AMP Response Element-Binding Protein
KW - Humans
KW - Immunohistochemistry
KW - Mice
KW - Mitogen-Activated Protein Kinases
KW - Myoblasts
KW - Neurons
KW - Phosphorylation
KW - Pick Disease of the Brain
KW - Precipitin Tests
KW - Staining and Labeling
KW - Transcription Factors
KW - p38 Mitogen-Activated Protein Kinases
KW - tau Proteins
U2 - 10.1007/s00401-003-0793-z
DO - 10.1007/s00401-003-0793-z
M3 - SCORING: Journal article
C2 - 14689204
VL - 107
SP - 185
EP - 189
JO - ACTA NEUROPATHOL
JF - ACTA NEUROPATHOL
SN - 0001-6322
IS - 3
ER -
