Selective inhibition of NF-κB activation prevents dopaminergic neuronal loss in a mouse model of Parkinson's disease

Anamitra Ghosh, Avik Roy, Xiaojuan Liu, Jeffrey H. Kordower, Elliott J. Mufson, Dean M. Hartley, Sankar Ghosh, R. Lee Mosley, Howard E. Gendelman, Kalipada Pahan

Research output: Contribution to journalArticle

279 Scopus citations

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Despite intense investigations, no effective therapy is available to stop its onset or halt its progression. The present study evaluates the ability of peptide corresponding to the NF-κB essential modifier-binding domain (NBD) of IκB kinase α(IKKα) or IKKβ to prevent nigrostriatal degeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD and establish a role for NF-κB in human parkinsonism. First, we found that NF-κB was activated within the substantia nigra pars compacta of PD patients and MPTP-intoxicated mice. However, i.p. injection of wild-type NBD peptide reduced nigral activation of NF-κB, suppressed nigral microglial activation, protected both the nigrostriatal axis and neurotransmitters, and improved motor functions in MPTP-intoxicated mice. These findings were specific because mutated NBD peptide had no effect. We conclude that selective inhibition of NF-κB activation by NBD peptide may be of therapeutic benefit for PD patients.

Original languageEnglish (US)
Pages (from-to)18754-18759
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number47
DOIs
StatePublished - Nov 20 2007

Keywords

  • MPTP
  • NBD peptides
  • Neurodegeneration

ASJC Scopus subject areas

  • General

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