Journal Article

DZNE-2020-07738

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png JNK plays a key role in tau hyperphosphorylation in Alzheimer's disease models.

Ploia, C. ; Antoniou, X. ; Sclip, A. ; Grande, V. ; Cardinetti, D. ; Colombo, A.DZNE* ; Canu, N. ; Benussi, L. ; Ghidoni, R. ; Forloni, G. ; Borsello, T. (Corresponding author)

2011
IOS Press Amsterdam

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Please use a persistent id in citations: doi:10.3233/JAD-2011-110320

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.

Keyword(s): Aged (MeSH) ; Aged, 80 and over (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Animals (MeSH) ; Cells, Cultured (MeSH) ; Cerebral Cortex: drug effects (MeSH) ; Cerebral Cortex: metabolism (MeSH) ; Cerebral Cortex: pathology (MeSH) ; Female (MeSH) ; Humans (MeSH) ; JNK Mitogen-Activated Protein Kinases: metabolism (MeSH) ; JNK Mitogen-Activated Protein Kinases: pharmacology (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Mitogen-Activated Protein Kinases: metabolism (MeSH) ; Neurofibrillary Tangles: drug effects (MeSH) ; Neurofibrillary Tangles: metabolism (MeSH) ; Neurofibrillary Tangles: pathology (MeSH) ; Neurons: drug effects (MeSH) ; Neurons: metabolism (MeSH) ; Neurons: pathology (MeSH) ; Phosphorylation (MeSH) ; Rats (MeSH) ; tau Proteins: metabolism (MeSH) ; tau Proteins ; JNK Mitogen-Activated Protein Kinases ; Mitogen-Activated Protein Kinases

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Contributing Institute(s):

1. Neuroproteomics (AG Lichtenthaler)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2011

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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