Novel signal transduction therapies for paralysis and pain | 48240

Journal of Neurology & Neurophysiology

ISSN - 2155-9562

Novel signal transduction therapies for paralysis and pain

3rd International Conference and Exhibition on Neurology & Therapeutics

September 08-10, 2014 Hilton Philadelphia Airport, USA

Chen Guang Yu

Scientific Tracks Abstracts: J Neurol Neurophysiol

Abstract :

Novel effective treatments for paralysis and chronic pain are urgently needed. The objectives of the study were to: 1) target individual ERK isoforms for neuroprotection, 2) identify cross-talk between ERK1/2 and calpain 1 for joint targeting, and 3) reduce B cell signal transduction for treatments of paralysis and pain. SiRNA/shRNA approach, fenbendazole treatment, molecular, histological, and behavioral assessments were used to develop therapies targeting these signal transduction and their interactions for spinal cord injury (SCI) and pain. Lentiviral-calpain 1 shRNA treatment was shown to reduce calpain 1 signaling and pathological/functional deficits after SCI in rats. ERK2 siRNA therapy and lentiviral ERK2 shRNA therapy revealed that ERK2 signaling is a novel pathological target after SCI and pain. ERK1 activation was previously shown to attenuate excitotoxic neuronal damage and neurodegeneration. Observations in calpain1-deficient mice and pharmacological intervention following SCI showed a cross-talk between calpain 1 and ERK1/2 (calpain 1 deficiency increased activation of ERK1/2, while ERK1/2 inhibition decreased calpain 1 expression following SCI). Pain behavioral assessment demonstrated that calpain 1 deficiency exacerbated SCI-Pain after excitotoxic SCI in mice. Fenbendazole treatments were shown to reduce B cell signaling pathway and improve pathological and functional recovery after SCI in mice. Taken together, these results demonstrate that siRNA/shRNA therapies targeting individual ERK isoform and their cross-talk with calpain 1 and fenbendazole/its analogs targeting B cell signaling pathways provide greater potential as novel therapeutics for paralysis, pain, and other neurological dysfunctions.

Biography :

Chen Guang Yu holds MD and PhD degrees. He completed Postdoctoral training at the University of Miami in 2000. He is currently Assistant Professor (Associate Professor, effective on April, 2014 at University of Kentucky. He has published more than 30 papers. He has also served as Associate Editor-in-Chief, Frontiers in Biology, Special Issue Editor, Journal of Spine, Scientist Reviewer on Grant Review Panels of USA Department of Defense (Pain Management 1 Award Panel and Neuroscience Grant Review Panel), and Reviewer for J Neurotrauma and other journals. His research focuses on identifying therapeutic targets and developing novel therapies for paralysis and pain.