The dual role of Cav1 channels in neurogenesis and neurodegeneration.

Risultato della ricerca: Contributo in rivistaContributo a convegno

Abstract

Calcium signals generated through Cav1 channels activate intracellular pathways affecting the expression of genes controlling cell death and differentiation. Aim of our study was to determine the role of Cav1 channel signals in the pathophysiology of neurodegenerative diseases, and their impact on neurogenesis. We demonstrated that the different neurotoxicity of amyloid-β protein (Aβ) variants found in the brains of Alzheimer's disease patients depends on their ability to upregulate Cav1 channel expression and activate Ca2+-dependent pro-apoptotic pathways (1,2). Cav1 channels also gave a prominent contribution to intracellular Ca2+ signals triggered by the binding of herpes simplex virus type 1 (HSV-1) to the plasma membrane of neurons. These HSV-1-induced Ca2+ signals promoted amyloid precursor protein (APP) phosphorylation and processing, with consequent intracellular and extracellular accumulation of Aβ and other neurotoxic APP fragments (3,4). In neural stem cells (NSC) up-regulation of Cav1 channel signals caused opposite effects, i.e., increased in vitro NSC differentiation toward the neuronal phenotype and enhanced adult hippocampal neurogenesis in vivo (5,6). These effects are mediated by Cav1 channel-depended phosphorylation of CREB and increased expression of the pro-neuronal genes Mash1, NeuroD and Hes1. Collectively, our findings suggest that modulation of Cav1 channel signals have the potential to counteract neurodegeneration and promote brain repair.
Lingua originaleEnglish
pagine (da-a)P48-P48
Numero di pagine1
RivistaActa Physiologica
Stato di pubblicazionePubblicato - 2011
EventoThe 62nd National Congress of the Italian Physiological Society - Sorrento
Durata: 25 set 201127 set 2011

Keywords

  • Amyloid beta protein
  • Apoptosis
  • Calcium signals
  • Differentiation
  • Electromagnetic fields
  • Neural Stem Cells

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