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In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
09:22

In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein

Published on: January 2, 2015

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

Cristina Ploia1, Xanthi Antoniou, Alessandra Sclip

  • 1Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.

Journal of Alzheimer'S Disease : JAD
|June 2, 2011
PubMed

Insights

c-Jun N-terminal kinases (JNKs) play a key role in Alzheimer's disease (AD) by promoting tau hyperphosphorylation. Inhibiting JNK with D-JNKI-1 reduced tau phosphorylation, suggesting JNK as a potential therapeutic target for AD.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Alzheimer's disease (AD) is a neurodegenerative disorder characterized by tau hyperphosphorylation and neurofibrillary tangle formation.
  • c-Jun N-terminal kinases (JNKs) are implicated in AD pathogenesis, being activated in AD brains and linked to amyloid plaque development.

Purpose of the Study:

  • To investigate the role of JNK in tau hyperphosphorylation in Alzheimer's disease.
  • To evaluate JNK as a potential therapeutic target for AD.

Main Methods:

  • Utilized a cell-permeable JNK inhibitor, D-JNKI-1.
  • Assessed JNK's effect on tau phosphorylation at specific sites (S202/T205, S422) in rat neuronal and human fibroblast cultures.
  • Evaluated D-JNKI-1 efficacy in an in vivo AD mouse model (TgCRND8).

Main Results:

  • D-JNKI-1 significantly reduced tau hyperphosphorylation at JNK target sites (S202/T205, S422) in neuronal and fibroblast cultures.
  • Inhibition of JNK by D-JNKI-1 decreased tau phosphorylation at S202/T205 in the TgCRND8 mouse model of AD.

Conclusions:

  • JNK signaling is fundamentally involved in regulating tau hyperphosphorylation.
  • Targeting JNK with inhibitors like D-JNKI-1 shows promise for therapeutic intervention in Alzheimer's disease.

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