Sonic Hedgehog Signaling and Hippocampal Neuroplasticity

If our fucking failures of stroke associations actually did anything, asking foundations or billionaires to support research on the sonic hedgehog pathway would be so easy.  Wouldn't you like to be able to promote yourself that you funded the research that solved the sonic hedgehog pathway in helping stroke survivors? But this won't occur because we have NO stroke leadership or strategy. FUCKING HEY!
 I started writing 4 blog posts about sonic hedgehog back in 2012. Yet we still have absolutely nothing done with it. 
http://www.sciencedirect.com/science/article/pii/S0166223616301382

• Pamela J. Yao^{1, ,} ,
• Ronald S. Petralia²,
• Mark P. Mattson^{1, 3, ,}

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http://dx.doi.org/10.1016/j.tins.2016.10.001

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Sonic hedgehog (Shh) is a secreted protein that controls the patterning of neural progenitor cells, and their neuronal and glial progeny, during development. Emerging findings suggest that Shh also has important roles in the formation and plasticity of neuronal circuits in the hippocampus, a brain region of fundamental importance in learning and memory. Shh mediates activity-dependent and injury-induced hippocampal neurogenesis. Activation of Shh receptors in the dendrites of hippocampal neurons engages a trans-neuronal signaling pathway that accelerates axon outgrowth and enhances glutamate release from presynaptic terminals. Impaired Shh signaling may contribute to the pathogenesis of several developmental and adult-onset neurological disorders that affect the hippocampus, suggesting a potential for therapeutic interventions that target Shh pathways.

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Trends

Shh regulates hippocampal stem cell proliferation and neuronal differentiation.

Cell responses to Shh are mediated by a membrane receptor (Patched), a transducer protein (Smoothened), and Gli transcription factors.

Regulation of axon elongation is a function of Shh in the developing and adult hippocampus.

Emerging findings suggest roles for Shh signaling in hippocampal synaptic plasticity.

Results of studies of animal models suggest potential therapeutic applications of Shh receptor agonists in several neurological disorders.