title: The flavanoide caffeic acid phenethyl ester blocks 6-hydroxydopamine-induced neurotoxicity.
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 microM) in a dose-dependent manner. Furthermore, CAPE was able to modulate the Ca(2+)-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.
authors.affiliation: Department of Neurology, Friedrich-Wilhelms-University, Bonn, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Noelker
authors.forename: Michael
authors.initials: M
authors.lastname: Bacher
authors.forename: Petra
authors.initials: P
authors.lastname: Gocke
authors.forename: Xing
authors.initials: X
authors.lastname: Wei
authors.forename: Thomas
authors.initials: T
authors.lastname: Klockgether
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Du
authors.forename: Richard
authors.initials: R
authors.lastname: Dodel
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western / Q000379:methods; D002109:Caffeic Acids / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D004347:Drug Interactions; D005452:Fluoresceins; D007150:Immunohistochemistry / Q000379:methods; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D016627:Oxidopamine / Q000633:toxicity*; D010300:Parkinson Disease / Q000209:etiology; D010506:Periodicals as Topic; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives; D011419:Propidium; D051381:Rats; D013997:Time Factors
chemical_list: D018663:Adrenergic Agents; D000975:Antioxidants; D002109:Caffeic Acids; D005452:Fluoresceins; D011419:Propidium; D016627:Oxidopamine; D045304:Cytochromes c; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; C018506:diacetylfluorescein