c-Jun N-terminal kinase regulates soluble Aβ oligomers and cognitive impairment in AD mouse model

Alessandra Sclip, Xanthi Antoniou, Alessio Colombo, Giovanni G. Camici, Laura Pozzi, Daniele Cardinetti, Marco Feligioni, Pietro Veglianese, Ferdinand H. Bahlmann, Luigi Cervo, Claudia Balducci, Cinzia Costa, Alessandro Tozzi, Paolo Calabresi, Gianluigi Forloni, Tiziana Borsello

Research output: Contribution to journalArticlepeer-review


Alzheimer disease (AD) is characterized by cognitive impairment that starts with memory loss to end in dementia. Loss of synapses and synaptic dysfunction are closely associated with cognitive impairment in AD patients. Biochemical and pathological evidence suggests that soluble Aβ oligomers correlate with cognitive impairment. Here, we used the TgCRND8 AD mouse model to investigate the role of JNK in long term memory deficits. TgCRND8 mice were chronically treated with the cell-penetrating c-Jun N-terminal kinase inhibitor peptide (D-JNKI1). D-JNKI1, preventing JNK action, completely rescued memory impairments (behavioral studies) as well as the long term potentiation deficits of TgCRND8 mice. Moreover, D-JNKI1 inhibited APP phosphorylation in Thr-668 and reduced the amyloidogenic cleavage of APP and Aβ oligomers in brain parenchyma of treated mice. In conclusion, by regulating key pathogenic mechanisms of AD, JNK might hold promise as innovative therapeutic target.

Original languageEnglish
Pages (from-to)43871-43880
Number of pages10
JournalJournal of Biological Chemistry
Issue number51
Publication statusPublished - Dec 23 2011

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology


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