Nicergoline, a drug used for age-dependent cognitive impairment, protects cultured neurons against β-amyloid toxicity

Filippo Caraci, Mariangela Chisari, Giuseppina Frasca, Pier Luigi Canonico, Angelo Battaglia, Marco Calafiore, Giuseppe Battaglia, Paolo Bosco, Ferdinando Nicoletti, Agata Copani, Maria Angela Sortino

Research output: Contribution to journalArticle

Abstract

Nicergoline, a drug used for the treatment of Alzheimer's disease and other types of dementia, was tested for its ability to protect neurons against β-amyloid toxicity. Pure cultures of rat cortical neurons were challenged with a toxic fragment of β-amyloid peptide (βAP25-35) and toxicity was assessed after 24 h. Micromolar concentrations of nicergoline or its metabolite, MDL, attenuated βAP25-35-induced neuronal death, whereas MMDL (another metabolite of nicergoline), the α1- adrenergic receptor antagonist, prazosin, or the serotonin 5HT-2 receptor antagonist, methysergide, were inactive. Nicergoline increased the basal levels of Bcl-2 and reduced the increase in Bax levels induced by β-amyloid, indicating that the drug inhibits the execution of an apoptotic program in cortical neurons. In mixed cultures of rat cortical cells containing both neurons and astrocytes, nicergoline and MDL were more efficacious than in pure neuronal cultures in reducing β-amyloid neurotoxicity. Experiments carried out in pure cultures of astrocytes showed that a component of neuroprotection was mediated by a mechanism of glial-neuronal interaction. The conditioned medium of cultured astrocytes treated with nicergoline or MDL for 72-96 h (collected 24 h after drug withdrawal) was neuroprotective when transferred to pure neuronal cultures challenged with β-amyloid. In cultured astrocytes, nicergoline increased the intracellular levels of transforming-growth factor-β and glial-derived neurotrophic factor, two trophic factors that are known to protect neurons against β-amyloid toxicity. These results raise the possibility that nicergoline reduces neurodegeneration in the Alzheimer's brain.

Original languageEnglish
Pages (from-to)30-37
Number of pages8
JournalBrain Research
Volume1047
Issue number1
DOIs
Publication statusPublished - Jun 14 2005

Keywords

  • β-Amyloid toxicity
  • Cortical neurons
  • Glial-neuronal interaction
  • Nicergoline

ASJC Scopus subject areas

  • Neuroscience(all)

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