The function of the neuronal proteins Shc and huntingtin in stem cells and neurons: pharmacologic exploitation for human brain diseases.
The identification of intracellular molecules and soluble factors that are important for neuronal differentiation and survival are of critical importance for development of therapeutic strategies for brain diseases. First, the activity of these factors/molecules may be enhanced in vivo in the attempt to induce proper neuronal differentiation and integration of the resident stem cells. Second, these factors may be applied ex vivo to increase the recovery of neurons from stem cells. Third, for those intracellular molecules that play crucial roles in neuronal survival, identification of their downstream targets may give us the chance to develop drug screening assays that use these targets for therapeutic purposes. In recent years, it has become evident that intracellular signaling processes are critical mediators of the responses of neural stem cells and neurons to growth factors. Analysis of the mechanisms of signal transduction has led to the striking finding that a handful of conserved signaling pathways appear to be used in different combinations to specify a wide variety of tissues or cells. This review will focus on the mechanisms by which specific molecules control the transition from proliferation to differentiation of neural progenitor cells and the subsequent survival of postmitotic neurons; it also discusses how this knowledge may be exploited to increase the potential efficacy of stem cell replacement in the damaged brain.
Zuccato
Chiara
C
Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milan, Milan, Italy.
Conti
Luciano
L
Reitano
Erika
E
Tartari
Marzia
M
Cattaneo
Elena
E
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D001927:Brain Diseases / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D002454:Cell Differentiation; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction / Q000502:physiology; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013234:Stem Cells / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1