JNK plays a key role in tau hyperphosphorylation in alzheimer's disease models

Cristina Ploia, Xanthi Antoniou, Alessandra Sclip, Valentina Grande, Daniele Cardinetti, Alessio Colombo, Nadia Canu, Luisa Benussi, Roberta Ghidoni, Gianluigi Forloni, Tiziana Borsello

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)315-329
Number of pages15
JournalJournal of Alzheimer's Disease
Volume26
Issue number2
DOIs
Publication statusPublished - 2011

Fingerprint

JNK Mitogen-Activated Protein Kinases
Alzheimer Disease
1-(3-trifluoromethylphenyl)-2-(N-(2-hydroxyethyl)amino)propane
Neurofibrillary Tangles
Amyloid Plaques
Disease Progression
Phosphotransferases
Fibroblasts
Peptides
Brain

Keywords

  • Alzheimer's disease
  • D-JNKI-1
  • JNK mitogen-activated protein kinases
  • phosphorylation
  • tau protein

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

Cite this

JNK plays a key role in tau hyperphosphorylation in alzheimer's disease models. / Ploia, Cristina; Antoniou, Xanthi; Sclip, Alessandra; Grande, Valentina; Cardinetti, Daniele; Colombo, Alessio; Canu, Nadia; Benussi, Luisa; Ghidoni, Roberta; Forloni, Gianluigi; Borsello, Tiziana.

In: Journal of Alzheimer's Disease, Vol. 26, No. 2, 2011, p. 315-329.

Research output: Contribution to journalArticle

Ploia, Cristina ; Antoniou, Xanthi ; Sclip, Alessandra ; Grande, Valentina ; Cardinetti, Daniele ; Colombo, Alessio ; Canu, Nadia ; Benussi, Luisa ; Ghidoni, Roberta ; Forloni, Gianluigi ; Borsello, Tiziana. / JNK plays a key role in tau hyperphosphorylation in alzheimer's disease models. In: Journal of Alzheimer's Disease. 2011 ; Vol. 26, No. 2. pp. 315-329.
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