The Hedgehog Pathway and Neurological Disorders.

Annu Rev Neurosci. 2006 Mar 24;

Authors: Dellovade T, Romer JT, Curran T, Rubin LL

The hedgehog pathway is a major regulator of embryonic development, and mutations that decrease its activity are known to be associated with severe defects in nervous system development. Recent evidence suggests hedgehog continues to function in adult tissue, normal as well as diseased, by regulating both cell proliferation and the production of growth and angiogenic factors. In the adult nervous system, this dual ability is especially important in regulating the behavior of neural stem and progenitor cells. This review summarizes information connecting hedgehog signaling and neural diseases, including neurodegenerative disorders and brain tumors, particularly medulloblastoma. We also describe the discovery and utility of small molecule agonists and antagonists of this pathway and their potential as novel types of therapeutics. Expected online publication date for the Annual Review of Neuroscience Volume 29 is June 16, 2006. Please see http://www.annualreviews.org/catalog/pub_dates.asp for revised estimates.

PMID: 16602907 [PubMed - as supplied by publisher]

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SUMMARY POINTS
1. Small molecule agonists and antagonists to the Hh pathway have been isolated and
characterized for use as therapeutics for CNS disorders and cancer, respectively.
2. Activation of the Hh pathway is neuroprotective and regenerative in models of PD,
stroke, and diabetic neuropathy.
3. Activation of the Hh pathway increases the proliferation and neuronal differentiation
of endogenous precursor cells in the adult brain.
FUTURE DIRECTIONS
1. The effects of Hh agonist–induced mobilization of endogenous stem cells on repair
and regeneration following CNS injury and disease should be explored.
2. The mechanism(s) of action for neuroprotective effects of Hh agonists should be
explored.

Curis published general articles