Smoothened, Stem Cell Maintenance and Brain Diseases

  • Martial RuatEmail author
  • Hélène Faure
  • Mathieu Daynac
Part of the Topics in Medicinal Chemistry book series (TMC, volume 16)


The Smoothened (Smo) receptor is a key transducer of the Sonic Hedgehog (Shh) signaling pathway in the brain. Recent studies in rodents have highlighted its major role in the maintenance of neural stem and progenitor cells in the two main neurogenic niches of the adult brain: the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus in the hippocampus. Smo may also regulate brain responses to various injuries, and its modulation in the primary cilia of brain cells is essential for regulating Shh signals. Recent clinical trials have underlined the therapeutic value of some Smo antagonists for the treatment of Hedgehog-linked medulloblastomas. Here, we review recent findings on the roles of Smo in the adult brain, and unravel research on the clinical implications for the treatment of brain diseases, that are increasingly under investigation.


Astrocytes Clinical trials Hedgehog Medulloblastoma Patched 



Activated neural stem cell


Alzheimer’s disease


Amyloid precursor protein


Central nervous system


Dentate Gyrus


Desert Hedgehog


Down syndrome


Epidermal growth factor receptor


Growth arrest-specific 1 protein


Granular cell layer


Cerebellar granule cell precursor


Glial cell line-derived neurotrophic factor


Glial fibrillary acidic protein


Astrocyte-specific glutamate transporter


G-protein-coupled receptor




Hedgehog-interacting protein


Indian Hedgehog


Joubert syndrome


Lysophosphatidyl choline


Lateral ventricle


Meckel syndrome


Neuron-glial antigen 2




Neural stem cell


Olfactory bulb




Oligodendrocyte precursor cell


Placental growth factor




Quiescent neural stem cell


Rostral migratory stream


Subgranular zone


Sonic Hedgehog


Aminoterminal fragment of Shh




Suppressor of fused


Subventricular zone


Transit-amplifying cell


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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.Molecules and Circuits Department, Signal Transduction and Developmental Neuropharmacology TeamNeuroPSI Institute, CNRS, UMR 9197Gif-sur-YvetteFrance

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