Calcium signals generated through Ca_v1 channels activate intracellular pathways affecting the expression of genes controlling cell death and differentiation. Aim of our study was to determine the role of Ca_v1 channel signals in the pathophysiology of neurodegenerative diseases, and their impact on neurogenesis.

We demonstrated that the different neurotoxicity of amyloid-b protein (Ab) variants found in the brains of Alzheimer's disease patients depends on their ability to up-regulate Ca_v1 channel expression and activate Ca²⁺-dependent pro-apoptotic pathways (1,2). Ca_v1 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 Ab and other neurotoxic APP fragments (3,4).

In neural stem cells (NSC) up-regulation of Ca_v1 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 Ca_v1 channel-depended phosphorylation of CREB and increased expression of the pro-neuronal genes Mash1, NeuroD and Hes1.

Collectively, our findings suggest that modulation of Ca_v1 channel signals have the potential to counteract neurodegeneration and promote brain repair.

References 

1. Piacentini et al., J Neurochem., 2008

2. Maiti et al., Biochem J., 2011

3. Piacentini et al., Neurobiol Aging, 2010

4. De Chiara et al., PLoS One, 2010

5. Piacentini et al., J Cell Phys., 2008

6. Cuccurazzu et al., Exp Neurol., 2010