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@ARTICLE{Ploia:141416,
author = {Ploia, Cristina and Antoniou, Xanthi and Sclip, Alessandra
and Grande, Valentina and Cardinetti, Daniele and Colombo,
Alessio and Canu, Nadia and Benussi, Luisa and Ghidoni,
Roberta and Forloni, Gianluigi and Borsello, Tiziana},
title = {{JNK} plays a key role in tau hyperphosphorylation in
{A}lzheimer's disease models.},
journal = {Journal of Alzheimer's disease},
volume = {26},
number = {2},
issn = {1875-8908},
address = {Amsterdam},
publisher = {IOS Press},
reportid = {DZNE-2020-07738},
pages = {315-329},
year = {2011},
abstract = {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.},
keywords = {Aged / Aged, 80 and over / Alzheimer Disease: metabolism /
Alzheimer Disease: pathology / Animals / Cells, Cultured /
Cerebral Cortex: drug effects / Cerebral Cortex: metabolism
/ Cerebral Cortex: pathology / Female / Humans / JNK
Mitogen-Activated Protein Kinases: metabolism / JNK
Mitogen-Activated Protein Kinases: pharmacology / Male /
Middle Aged / Mitogen-Activated Protein Kinases: metabolism
/ Neurofibrillary Tangles: drug effects / Neurofibrillary
Tangles: metabolism / Neurofibrillary Tangles: pathology /
Neurons: drug effects / Neurons: metabolism / Neurons:
pathology / Phosphorylation / Rats / tau Proteins:
metabolism / tau Proteins (NLM Chemicals) / JNK
Mitogen-Activated Protein Kinases (NLM Chemicals) /
Mitogen-Activated Protein Kinases (NLM Chemicals)},
cin = {AG Lichtenthaler},
ddc = {610},
cid = {I:(DE-2719)1110006},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:21628793},
doi = {10.3233/JAD-2011-110320},
url = {https://pub.dzne.de/record/141416},
}