Testing NF-kB-based therapy in hemiparkinsonian monkeys

Susanta Mondal, Avik Roy, Arundhati Jana, Sankar Ghosh, Jeffrey H. Kordower, Kalipada Pahan

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Parkinson's disease (PD) is the most common human neurodegenerative disorder affecting movement, balance, flexibility, and coordination. Despite intense investigation, no effective therapy is available to stop the onset PD or halt its progression. The primate model of PD is considered to be one of the best available models for human PD. Since neuroinflammation plays an important role in the pathogenesis of PD and NF-kB, a proinflammatory transcription factor, participates in the transcription of many proinflammatory molecules, this study evaluates the ability of a peptide corresponding to the NF-kB essential modifier (NEMO)-binding domain (NBD) of I?B kinase (IKK)a or IKKβ to protect dopaminergic neurons in hemiparkinsonian monkeys. First, we found that NF-kB was activated within the substantia nigra pars compacta of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated hemiparkinsonian monkeys. However, intramuscular injection of wild type NBD (wtNBD) peptide reduced nigral activation of NF-kB and expression of inducible nitric oxide synthase, protected both the nigrostriatal axis and neurotransmitters, and improved motor functions in hemiparkinsonian monkeys. These findings were specific as mutated NBD peptide did not exhibit such effects. These results may help in the translation of NF-kB-based therapy to PD clinics.

Original languageEnglish (US)
Pages (from-to)544-556
Number of pages13
JournalJournal of Neuroimmune Pharmacology
Volume7
Issue number3
DOIs
StatePublished - Sep 2012
Externally publishedYes

Keywords

  • Dopamine
  • Dopaminergic neurons
  • Monkey
  • Motor function
  • NF-kB
  • Parkinson's disease

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

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