The flavanoide caffeic acid phenethyl ester blocks 6-hydroxydopamine- induced neurotoxicity

Carmen Noelker, Michael Bacher, Petra Gocke, Xing Wei, Thomas Klockgether, Yansheng Du, Richard Dodel

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic (DA) neurons of the substantia nigra pars compacta. 6-Hydroxydopamine (6-OHDA) is specific to dopaminergic neurons in intrastriatal rodent models. It induces neuronal death either via uncoupling mitochondrial oxidative phosphorylation resulting in energy deprivation or alternatively, is associated with its ability to produce hydrogen peroxide, hydroxyl and superoxide radicals. Caffeic acid phenethyl ester (CAPE), an antioxidant flavanoid, has antiviral, anti-inflammatory, antioxidant, and immunomodulatory properties. Recent studies have shown that CAPE has also a neuroprotective effects in ischemia and low potassium-induced neuronal apoptotic models. In cerebellar granule neurons CAPE significantly blocks 6-OHDA mediated cell death (70 μM) in a dose-dependent manner. Furthermore, CAPE was able to modulate the Ca2+-induced release of cyctochrome c in isolated liver mitochondria. Caspase-3 activation following 6-OHDA treatment was markedly inhibited in the presence of CAPE. Although the molecular mechanisms associated with CAPE's neuroprotective effects remain to be elucidated in more detail, our results clearly demonstrate a considerable neuroprotective effect of CAPE. Since a mitochondrial insult is a major cause for the degeneration of nigral neurons in PD, we hypothesize that propolis derivatives, in particular CAPE, may have a neuroprotective effect on those cells and may be a promising drug candidate to be taken into in vivo models of PD.

Original languageEnglish
Pages (from-to)39-43
Number of pages5
JournalNeuroscience Letters
Volume383
Issue number1-2
DOIs
StatePublished - Jul 22 2005

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Oxidopamine
Neuroprotective Agents
Parkinson Disease
Dopaminergic Neurons
Antioxidants
Propolis
Nerve Degeneration
Liver Mitochondrion
Oxidative Phosphorylation
Substantia Nigra
caffeic acid phenethyl ester
Superoxides
Caspase 3
Neurodegenerative Diseases
Hydroxyl Radical
Hydrogen Peroxide
Antiviral Agents
Rodentia
Potassium
Cell Death

Keywords

  • 6-OHDA
  • Apoptosis
  • CAPE
  • Caspase-3
  • Cytochrome c
  • Parkinson's disease

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

The flavanoide caffeic acid phenethyl ester blocks 6-hydroxydopamine- induced neurotoxicity. / Noelker, Carmen; Bacher, Michael; Gocke, Petra; Wei, Xing; Klockgether, Thomas; Du, Yansheng; Dodel, Richard.

In: Neuroscience Letters, Vol. 383, No. 1-2, 22.07.2005, p. 39-43.

Research output: Contribution to journalArticle

Noelker, C, Bacher, M, Gocke, P, Wei, X, Klockgether, T, Du, Y & Dodel, R 2005, 'The flavanoide caffeic acid phenethyl ester blocks 6-hydroxydopamine- induced neurotoxicity', Neuroscience Letters, vol. 383, no. 1-2, pp. 39-43. https://doi.org/10.1016/j.neulet.2005.04.023
Noelker, Carmen ; Bacher, Michael ; Gocke, Petra ; Wei, Xing ; Klockgether, Thomas ; Du, Yansheng ; Dodel, Richard. / The flavanoide caffeic acid phenethyl ester blocks 6-hydroxydopamine- induced neurotoxicity. In: Neuroscience Letters. 2005 ; Vol. 383, No. 1-2. pp. 39-43.
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