Columbia University

Ying-Ju Sung

Donald W Landry

Shi-Xian Deng

Richard Ambron

Jeremy Robert Greenwood

Yuli Xie

Leah Lynn Frye

Shi-Zian Deng

The present invention relates to the discovery of a novel molecular pathway involved in long-term hyperexcitability of sensory neurons, which, in higher animals, is associated with persistent pain. It is based on the discovery that, following injury to an axon of a neuron, an increase in nitric oxide synthase activity results in increased nitric oxide production, which, in turn, activates guanylyl cyclase, thereby increasing levels of cGMP. Increased cGMP results in activation of protein kinase G ('PKG'), which then is retrogradely transported along the axon to the neuron cell body, where it phosphorylates MAPKerk.

Neuronal pain pathway

The present invention relates to compounds that may be used to inhibit activation of protein kinase G ('PKG'). It is based, at least in part, on the discovery of the tertiary structure of PKG and the identification of molecules that either bind to the active site of PKG and/or are analogs of balanol.

Neuronal pain pathway modulators

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Prospect Park, NJ, United States of America

Ying-Ju Sung