TY  - JOUR
AU  - Ploia, Cristina
AU  - Antoniou, Xanthi
AU  - Sclip, Alessandra
AU  - Grande, Valentina
AU  - Cardinetti, Daniele
AU  - Colombo, Alessio
AU  - Canu, Nadia
AU  - Benussi, Luisa
AU  - Ghidoni, Roberta
AU  - Forloni, Gianluigi
AU  - Borsello, Tiziana
TI  - JNK plays a key role in tau hyperphosphorylation in Alzheimer's disease models.
JO  - Journal of Alzheimer's disease
VL  - 26
IS  - 2
SN  - 1875-8908
CY  - Amsterdam
PB  - IOS Press
M1  - DZNE-2020-07738
SP  - 315-329
PY  - 2011
AB  - Alzheimer's disease (AD) is a major clinical concern, and the search for new molecules to combat disease progression remains important. One of the major hallmarks in AD pathogenesis is the hyperphosphorylation of tau and subsequent formation of neurofibrillary tangles. Several kinases are involved in this process. Amongst them, c-Jun N-terminal kinases (JNKs) are activated in AD brains and are also associated with the development of amyloid plaques. This study was designed to investigate the contribution of JNK in tau hyperphosphorylation and whether it may represent a potential therapeutic target for the fight against AD. The specific inhibition of JNK by the cell permeable peptide D-JNKI-1 led to a reduction of p-tau at S202/T205 and S422, two established target sites of JNK, in rat neuronal cultures and in human fibroblasts cultures. Similarly, D-JNKI-1 reduced p-tau at S202/T205 in an in vivo model of AD (TgCRND8 mice). Our findings support the fundamental role of JNK in the regulation of tau hyperphosphorylation and subsequently in AD pathogenesis.
KW  - Aged
KW  - Aged, 80 and over
KW  - Alzheimer Disease: metabolism
KW  - Alzheimer Disease: pathology
KW  - Animals
KW  - Cells, Cultured
KW  - Cerebral Cortex: drug effects
KW  - Cerebral Cortex: metabolism
KW  - Cerebral Cortex: pathology
KW  - Female
KW  - Humans
KW  - JNK Mitogen-Activated Protein Kinases: metabolism
KW  - JNK Mitogen-Activated Protein Kinases: pharmacology
KW  - Male
KW  - Middle Aged
KW  - Mitogen-Activated Protein Kinases: metabolism
KW  - Neurofibrillary Tangles: drug effects
KW  - Neurofibrillary Tangles: metabolism
KW  - Neurofibrillary Tangles: pathology
KW  - Neurons: drug effects
KW  - Neurons: metabolism
KW  - Neurons: pathology
KW  - Phosphorylation
KW  - Rats
KW  - tau Proteins: metabolism
KW  - tau Proteins (NLM Chemicals)
KW  - JNK Mitogen-Activated Protein Kinases (NLM Chemicals)
KW  - Mitogen-Activated Protein Kinases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:21628793
DO  - DOI:10.3233/JAD-2011-110320
UR  - https://pub.dzne.de/record/141416
ER  -