The Function of the Neuronal Proteins Shc and Huntingtin in Stem Cells and Neurons: Pharmacologic Exploitation for Human Brain Diseases

doi:10.1196/annals.1334.006

^aThese authors contributed equally to this manuscript and should be considered co-first authors.
Address for correspondence: Elena Cattaneo, Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milan, Milan, Italy. Voice: +39-02-5031 8333; fax:+39-02-5031 8284. Elena.Cattaneo{at}unimi.it

The identification of intracellular molecules and soluble factorsthat are important for neuronal differentiation and survivalare of critical importance for development of therapeutic strategiesfor brain diseases. First, the activity of these factors/moleculesmay be enhanced in vivo in the attempt to induce proper neuronaldifferentiation and integration of the resident stem cells.Second, these factors may be applied ex vivo to increase therecovery of neurons from stem cells. Third, for those intracellularmolecules that play crucial roles in neuronal survival, identificationof their downstream targets may give us the chance to developdrug screening assays that use these targets for therapeuticpurposes. In recent years, it has become evident that intracellularsignaling processes are critical mediators of the responsesof neural stem cells and neurons to growth factors. Analysisof the mechanisms of signal transduction has led to the strikingfinding that a handful of conserved signaling pathways appearto be used in different combinations to specify a wide varietyof tissues or cells. This review will focus on the mechanismsby which specific molecules control the transition from proliferationto differentiation of neural progenitor cells and the subsequentsurvival of postmitotic neurons; it also discusses how thisknowledge may be exploited to increase the potential efficacyof stem cell replacement in the damaged brain.