Recent Advances in Neurogenic Small Molecules as Innovative Treatments for Neurodegenerative Diseases.
The central nervous system of adult mammals has long been considered as a complex static structure unable to undergo any regenerative process to refurbish its dead nodes. This dogma was challenged by Altman in the 1960s and neuron self-renewal has been demonstrated ever since in many species, including humans. Aging, neurodegenerative, and some mental diseases are associated with an exponential decrease in brain neurogenesis. Therefore, the controlled pharmacological stimulation of the endogenous neural stem cells (NSCs) niches might counteract the neuronal loss in Alzheimer's disease (AD) and other pathologies, opening an exciting new therapeutic avenue. In the last years, druggable molecular targets and signalling pathways involved in neurogenic processes have been identified, and as a consequence, different drug types have been developed and tested in neuronal plasticity. This review focuses on recent advances in neurogenic agents acting at serotonin and/or melatonin systems, Wnt/β-catenin pathway, sigma receptors, nicotinamide phosphoribosyltransferase (NAMPT) and nuclear erythroid 2-related factor (Nrf2).
Instituto de Química Médica, Consejo Superior de Investigaciones Científicas (IQM-CSIC), C/Juan de la Cierva 3, Madrid 28006, Spain. clherrer@iqm.csic.es.
Clara
C
Herrera-Arozamena
Instituto de Química Médica, Consejo Superior de Investigaciones Científicas (IQM-CSIC), C/Juan de la Cierva 3, Madrid 28006, Spain. olaia.marti.mari@gmail.com.
Olaia
O
Martí-Marí
Instituto de Química Médica, Consejo Superior de Investigaciones Científicas (IQM-CSIC), C/Juan de la Cierva 3, Madrid 28006, Spain. mhestradav@iqm.csic.es.
Martín
M
Estrada
Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA. mario.delafuenterevenga@vcuhealth.org.
Mario
M
de la Fuente Revenga
Instituto de Química Médica, Consejo Superior de Investigaciones Científicas (IQM-CSIC), C/Juan de la Cierva 3, Madrid 28006, Spain. isabelrguez@iqm.csic.es.
María Isabel
MI
Rodríguez-Franco
D000818:Animals; D006801:Humans; D058953:Neural Stem Cells / Q000378:metabolism* / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D055495:Neurogenesis / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000627:therapeutic use*
D018696:Neuroprotective Agents
Wnt/β-catenin pathway; adult neurogenesis; melatonin receptors; nicotinamide phosphoribosyltransferase; nuclear erythroid 2-related factor; serotonin system; sigma receptors