Snapshot Issue 13 August 2005
Sonic hedgehog protein
Animals have such a keen sense of smell that in most instances they are literally led by their noses. In humans, however, such a sense seems to be more of a luxury than a necessity. Despite this, the mechanisms underlying human olfactory perception have been under close scrutiny for decades. Indeed, one part of our brain – the olfactive bulb – which is in effect the relay between our nose and our brain happens to be supplied with brand-new neurons on a daily basis. Surprisingly, these novel neurons do not come from the olfactive bulb itself but result from stem cells in a cerebral zone termed the subventricular zone. Stem cells are by far not specific to the olfactory system; many other adult organs regenerate cells which are defective. So far though, no one knows what kind of role the olfactory stem cells have.
What we do know though is that neurogenesis is orchestrated by proteins. One in particular – the Sonic Hedgehog protein or SHH protein – seems to have a major role. In embryos, it plays a crucial role in brain development. In undifferentiated cells, its amino-acid sequence is cleaved in two and cholesterol promptly added to one of the fragments. Both operations – i.e. the cleaving and the addition of cholesterol – are carried out by the same protein: SHH itself! In this cleaved and decorated state, SHH leaves the cell and diffuses – sonic diffusion? – as a hexamer towards the stem cells where it binds to membrane receptors. Receptor-binding leads to the activation of transcription factors known as the GLI proteins which in turn trigger off the process of neurogenesis.
Can other regions of the brain supply adults with new neurons? And via SHH? Yes. Sonic hedgehog protein is not exclusive to the olfactory system and also supplies the hippocampus – our memory center – with brand-new cells… SHH stimulation of neurogenesis in adults is – to say the least – of great interest. Imagine the capacity of someone hit by Parkinson’s disease to self-supply a bottomless pit of neurons to counter neuronal loss. A Godsend. However, before daring to believe in this kind of therapy, researchers need a detailed understanding of how SHH acts in olfactory neurogenesis. Such an adventure is being undertaken by two Swiss teams – the one from Geneva lead by Professor Ariel Ruiz i Altaba and the other from Lausanne lead by Dr Alan Carleton – who were jointly awarded the Leenaards 2005 prize. To be continued…
Zinc finger protein GLI 1, Mus musculus (mouse): P47806
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