title: Caffeic acid phenethyl ester (CAPE) protects PC12 cells from MPP+ toxicity by inducing the expression of neuron-typical proteins.
abstract: Neurite loss is an early event in neurodegenerative diseases; therefore, the regeneration of the network of neurites constitutes an interesting strategy of treatment for such disorders. Neurotrophic factors play a critical role in neuronal regeneration, but their clinical use is limited by their inability to cross the blood brain barrier. Oxidative and inflammatory events are implicated in neurodegeneration and antioxidant compounds have been suggested as potential neuroprotectors. The protective potential of CAPE (caffeic acid phenethyl ester) has been shown in different models of neurotoxicity (in vitro and in vivo) and it has been associated with immune-modulatory, antioxidant and anti-inflammatory properties; however, other mechanisms might be involved. The present study demonstrates that CAPE protects PC12 cells from the cellular death induced by the dopaminergic neurotoxin MPP(+) by increasing the network of neurites. Results showed that CAPE induced the formation, elongation and ramification of neurites in PC12 cells non-stimulated with NGF (nerve growth factor) and inhibited the shortage of neurites induced by the dopaminergic neurotoxin. These effects were associated with increased expression of neuron-typical proteins responsible for axonal growth (GAP-43) and synaptogenesis (synaptophysin and synapsin I). It is noteworthy that, unlike neurotrophins, CAPE would be able to cross the blood brain barrier and exert its neurotrophic effects in the brain. This study corroborates the therapeutic potential of CAPE in neurodegenerative diseases while proposes the involvement of neuroplasticity in the mechanism of neuroprotection.
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: acsantos@fcfrp.usp.br.
authors.forename: Neife Aparecida Guinaim
authors.initials: NA
authors.lastname: dos Santos
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Nádia Maria
authors.initials: NM
authors.lastname: Martins
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Roberto de Barros
authors.initials: Rde B
authors.lastname: Silva
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Rafaela Scalco
authors.initials: RS
authors.lastname: Ferreira
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Flávia Malvestio
authors.initials: FM
authors.lastname: Sisti
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Antonio Cardozo
authors.initials: AC
authors.lastname: dos Santos
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D002109:Caffeic Acids / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019922:GAP-43 Protein / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism; D016501:Neurites / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016716:PC12 Cells; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051381:Rats; D016704:Synapsins / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D002109:Caffeic Acids; D019922:GAP-43 Protein; D018696:Neuroprotective Agents; D016704:Synapsins; D016708:Synaptophysin; C569016:Syp protein, rat; D020932:Nerve Growth Factor; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; D015655:1-Methyl-4-phenylpyridinium
keywords: CAPE (caffeic acid phenethyl ester); GAP-43; Neuroprotection; Synapsin I; Synaptophysin