Novel nuclear factor-KappaB targeting peptide suppresses β-amyloid induced inflammatory and apoptotic responses in neuronal cells

Mythily Srinivasan, Baindu Bayon, Nipun Chopra, Debomoy Lahiri

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

In the central nervous system (CNS), activation of the transcription factor nuclear factorkappa B (NF-κβ) is associated with both neuronal survival and increased vulnerability to apoptosis. The mechanisms underlying these dichotomous effects are attributed to the composition of NF-κB dimers. In Alzheimer's disease (AD), β-amyloid (Aβ) and other aggregates upregulate activation of p65:p50 dimers in CNS cells and enhance transactivation of pathological mediators that cause neuroinflammation and neurodegeneration. Hence selective targeting of activated p65 is an attractive therapeutic strategy for AD. Here we report the design, structural and functional characterization of peptide analogs of a p65 interacting protein, the glucocorticoid induced leucine zipper (GILZ). By virtue of binding the transactivation domain of p65 exposed after release from the inhibitory IκB proteins in activated cells, the GILZ analogs can act as highly selective inhibitors of activated p65 with minimal potential for off-target effects.

Original languageEnglish (US)
Article numbere0160314
JournalPLoS One
Volume11
Issue number10
DOIs
StatePublished - Oct 1 2016

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Leucine Zippers
transcription factor NF-kappa B
leucine zipper
Neurology
transcriptional activation
amyloid
Alzheimer disease
glucocorticoids
Amyloid
Dimers
Transcriptional Activation
Glucocorticoids
central nervous system
Alzheimer Disease
Central Nervous System
neurons
Chemical activation
peptides
Peptides
protein aggregates

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Novel nuclear factor-KappaB targeting peptide suppresses β-amyloid induced inflammatory and apoptotic responses in neuronal cells. / Srinivasan, Mythily; Bayon, Baindu; Chopra, Nipun; Lahiri, Debomoy.

In: PLoS One, Vol. 11, No. 10, e0160314, 01.10.2016.

Research output: Contribution to journalArticle

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