Neuroglobin and neuronal cell survival

Marco Fiocchetti, Elisabetta De Marinis, Paolo Ascenzi, Maria Marino

Research output: Contribution to journalArticle

Abstract

The balance between neuronal apoptosis and survival sculpts the developing brain and has an important role in neurodegenerative diseases. Thus, the individuation of signals that could modulate the cell death machinery as well as enhance survival in neurons promises to provide multiple points of therapeutic intervention in neurode-generative diseases. Neuroglobin (NGB), thefirst nerve globin identified in neuronal tissues of humans, seems to possess a protective role in the brain only after up-regulation. Here, the NGB physiological role in the control of neuronal survival is reviewed. In vitro studies suggested that cytosolic NGB could react very rapidly with cytochrome c released from mitochondria, thus interfering with the intrinsic pathway of apoptosis. Although very suggestive, these data do not explain either the role of NGB up-regulation in neuroprotection or the recently reported NGB localization into mitochondria. Recently, we identified the steroid hormone 17β-estradiol (E2) as an endogenous modulator of NGB levels in neuroblastoma SK-N-BE cell line. Upon E2 stimulation, NGB reallocates mainly into mitochondria where the association with the mitochondrial cytochrome c occurs. Remarkably, E2 treatment before an apoptotic stimulus strongly enhances the NGB:cytochrome c association reducing cytochrome c release into the cytosol. As a consequence, adecrease of caspase-3 activation and, inturn, of the apoptotic cascade activation take place. Besides E2, other compounds have been reported to up-regulate the NGB expression highlighting the possibility to develop NGB-mediated therapeutic strategies against stroke damage and neurodegenerative diseases. This article is part of a Special Issue entitled: Oxygen Binding and Sensing Proteins.

Original languageEnglish
Pages (from-to)1744-1749
Number of pages6
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1834
Issue number9
DOIs
Publication statusPublished - 2013

Keywords

  • Apoptosis
  • Neuroglobin
  • Neuroprotection
  • Signal transduction pathways

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Analytical Chemistry
  • Molecular Biology
  • Medicine(all)

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