Targeting the JAK2/STAT3 axis in Alzheimer's disease

Tomohiro Chiba, Marina Yamada, Sadakazu Aiso

Research output: Contribution to journalReview article

54 Citations (Scopus)

Abstract

Background: Amyloid aβ (Aaβ) has long been implicated in the pathogenesis of Alzheimer's disease (AD). Little is known, however, about the intracellular events in neurons which lead to memory loss related to AD. Focusing on the fact that an AD-specific neuroprotective peptide named humanin (HN) inhibits AD-related neurotoxicity by activating the JAK2/STAT3 signaling axis, we recently found that age- and disease-dependent deterioration in the JAK2/STAT3 axis plays a critical role in the pathogenesis of AD. Objective/methods: Here we summarize the neuroprotective effect of HN and its derivative, named colivelin (CLN), and also review the roles of the JAK2/STAT3 axis in memory impairment related to AD. Results/conclusions: The JAK2/STAT3 axis is a major transducer of HN-mediated neuroprotective activity. Aâ-dependent inactivation of the JAK2/STAT3 axis in hippocampal neurons causes cholinergic dysfunction via pre- and post-synaptic mechanisms, which leads to memory impairment related to AD. This provides not only a novel pathological hallmark of AD but also a novel target in AD therapy.

Original languageEnglish
Pages (from-to)1155-1167
Number of pages13
JournalExpert Opinion on Therapeutic Targets
Volume13
Issue number10
DOIs
Publication statusPublished - 2009 Oct 1
Externally publishedYes

Fingerprint

Data storage equipment
Neurons
Neuroprotective Agents
Amyloid
Cholinergic Agents
Deterioration
Transducers
Derivatives
Peptides
humanin

Keywords

  • Alzheimer's disease (AD)
  • Colivelin (CLN)
  • Humanin (HN)
  • Janus kinase 2 (JAK2)
  • Memory impairment
  • Neuroprotection
  • Signal transducer and activator of transcription 3 (STAT3)

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

Targeting the JAK2/STAT3 axis in Alzheimer's disease. / Chiba, Tomohiro; Yamada, Marina; Aiso, Sadakazu.

In: Expert Opinion on Therapeutic Targets, Vol. 13, No. 10, 01.10.2009, p. 1155-1167.

Research output: Contribution to journalReview article

Chiba, Tomohiro ; Yamada, Marina ; Aiso, Sadakazu. / Targeting the JAK2/STAT3 axis in Alzheimer's disease. In: Expert Opinion on Therapeutic Targets. 2009 ; Vol. 13, No. 10. pp. 1155-1167.
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