Journal of NeuroVirology

, Volume 18, Issue 6, pp 445–455 | Cite as

Catechins protect neurons against mitochondrial toxins and HIV proteins via activation of the BDNF pathway

  • Samir Nath
  • Muznabanu Bachani
  • Deepti Harshavardhana
  • Joseph P. Steiner
Article

Abstract

Currently, there is no effective treatment for neurological complications of infection with the human immunodeficiency virus that persists despite the use of combination antiretroviral therapy. A medium throughput assay was developed for screening neuroprotective compounds using primary mixed neuronal cells and mitochondrial toxin 3-nitropropionic acid. Using this assay, a library of 2,000 compounds was screened. Out of 256 compounds that showed variable degrees of neuroprotection, nine were related to epicatechin, a monomeric flavonoid found in cocoa and green tea leaves that readily crosses the blood–brain barrier. Hence, catechin, epicatechin, and the related compound, epigallocatechin gallate (EGCG) were further screened for their neuroprotective properties against HIV proteins Tat and gp120, and compared to those of resveratrol. Epicatechin and EGCG targets the brain-derived neurotrophic factor (BDNF) and its precursor proBDNF signaling pathways, normalizing both Tat-mediated increases in proapoptotic proBDNF and concomitant Tat-mediated decreases in the mature BDNF protein in hippocampal neurons. Epicatechin and epigallocatechin gallate were more potent than catechin or resveratrol as neuroprotectants. Due to its simpler structure and more efficient blood–brain barrier penetration properties, epicatechin might be the best therapeutic candidate for neurodegenerative diseases including HIV-associated neurocognitive disorders where oxidative stress is an important pathophysiological mechanism.

Keywords

Catechins Neurons Mitochondrial toxins BDNF pathway 

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Copyright information

© Journal of NeuroVirology, Inc. (outside the USA) 2012

Authors and Affiliations

  • Samir Nath
    • 1
  • Muznabanu Bachani
    • 1
  • Deepti Harshavardhana
    • 1
  • Joseph P. Steiner
    • 1
    • 2
  1. 1.Department of NeurologyJohns Hopkins UniversityBaltimoreUSA
  2. 2.Neurotherapeutics Development UnitNINDS Translational Neuroscience CenterBethesdaUSA

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