International Conference on Brain Disorders and Therapeutics August 24-26, 2015 London, UK

Biography:

Pant received his M.A. and Ph.D. degrees in Physics from Agra University, Agra, India. His postdoctoral studies were conducted on the mechanisms of electron and ion transport in model membrane systems at the Department of Biophysics at Michigan State University. He joined the Laboratory of Neurobiology in the NIMH as a senior staff fellow in 1974 with Dr. Ichiji Tasaki where he studied the function of the axonal cytoskeleton in the squid giant axon. In 1979 he moved to the NIAAA extending his studies on the neuronal cytoskeleton and the effects of alcohol on its regulation. Dr. Pant moved to the NINDS, Laboratory of Neurochemistry in 1987 where he is presently chief of the section on Cytoskeleton Regulation. His laboratory is studying the mechanisms of topographic regulation of neuronal cytoskeleton proteins by post-translational modification, including the role of kinase cascades in normal brain and during neurodegeneration.

Abstract:

Besides the hallmark pathology of amyloid plaques and neurofibrillary tangles (NFTs), it has been now well documented thatrncyclin-dependent kinase 5 (Cdk5), a critical neuronal kinase in nervous system development, function and survival whenrnderegulated and hyperactivated induces AD and ALS like phenotypes in mice. Under physiological conditions, Cdk5 activity isrntightly regulated. The deregulation and hyperactivation of Cdk5/p25 due to neuronal insults and toxicity induces neuropathology.rnThus Cdk5/p25 becomes prime therapeutic target for AD and other neurodegenerative diseases associated with the hyperactivationrnof Cdk5. In order to prevent hyperactivation of Cdk5/p25, we have designed several small peptides of p25 on the basis of Cdk5/rnp25 crystal structure and molecular modeling, evaluated for competition with p25 and thus inhibiting selectively the hyperactivityrnof Cdk5. We discovered a small peptide (p5) comprising of 24 amino acids inhibited Cdk5 hyperactivation. The modified of p5rnto TFP5 crosses blood brain barrier (BBB) and was examined its therapeutic role in transgenic AD and ALS model mice. The p25rntransgenic AD model (p25Tg) and 5XFAD mice were chosen since these mice show similar phenotypes to AD patients. Post TFP5rninjections in p25Tg mice, 5XFAD and ALS model mice displayed significant reduction in Cdk5/p25 hyperactivity, Aβ plaquernformation along with behavioral rescue. TFP5 does not inhibit normal Cdk5/p35 activity and therefore has no toxic side effects.rnIn addition, treated mice rescued synaptic dysfunction, neuroinflammation and a reduction in phospho-neurofilaments/tau andrnneuronal cell death. These results indicate that TFP5 has a potential role as a therapeutic candidate for AD, ALS and other relatedrnneurological diseases.

Biography:

Wayne Grant Carter received his Honours degree and PhD in Biochemistry from the University of Southampton, studying protein post-translational modification and\\\\r\\\\nmolecular signalling cascades. He is currently a Group Leader in the School of Medicine, University of Nottingham, with research focused upon protein post-translational\\\\r\\\\nmodification and molecular mechanisms of hepato- and neuro-toxicity. His recent publication detailing “alcohol-related brain damage in humans” (PLoS ONE 9(4): e93586)\\\\r\\\\nreceived considerable national and international media coverage

Abstract:

The mechanism by which neurotoxicants, such as alcohol, damage neurons is not fully understood. To investigate the\\\\r\\\\nneuropathology arising from cumulative excessive alcohol consumption we examined prefrontal cortex brain tissue from human\\\\r\\\\nalcoholics and age, gender, and post-mortem delay matched control subjects. H&E staining and light microscopy of prefrontal\\\\r\\\\ncortex tissue revealed a reduction in the levels of cytoskeleton surrounding the nuclei of cortical and subcortical neurons, and a\\\\r\\\\ndisruption of subcortical neuron patterning in alcoholic subjects. One dimensional polyacrylamide gel electrophoresis proteomics\\\\r\\\\nof cytosolic proteins identified dramatic reductions in the protein levels of spectrin β II, and α- and β-tubulins in alcoholics, and\\\\r\\\\nthese were validated and quantitated by Western blotting. In alcoholics, significant loss of cytosolic α- and β-tubulins was also\\\\r\\\\nseen in the other brain regions examined: caudate nucleus, hippocampus, and cerebellum. We have also extended our studies to\\\\r\\\\nassess brain damage in rats administered alcohol for a 4-week period. Results of this short-term (acute) alcohol exposure will also\\\\r\\\\nbe discussed.

Biography:

Mark S. Kindy, Ph.D. is Professor of Neurosciences at the Medical University of South Carolina, Adjunct Professor of Bioengineering at Clemson University, Adjunct Professor of Chemical Engineering at the University of South Carolina, Adjunct Professor of Management and Entreprenurialism, School of Business, College of Charleston. He received his BA in zoology from the University of Massachusetts in 1980. Dr. Kindy received his Ph.D. in Biochemistry from Boston University School of Medicine from 1982-1987. He was a post-doctoral fellow at the Salk Institute from 1987-1989 in Molecular Biology and Virology. From 1989-2002, Dr. Kindy was a faculty member in the Department of Biochemistry at the University of Kentucky and rose from Assistant Professor to Full Professor. Dr. Kindy is currently the Admiral Pihl Endowed Professor in the Department of Neurosciences. Dr. Kindy is also a Research Career Scientist at the Ralph H. Johnson VA Medical Center in Charleston. Dr. Kindy has served on many NIH, AHA, AA review panels, has reviewed for many journals and is currently on the editorial board of 10 journals. Dr. Kindy has over 140 peer reviewed publications and is funded by the NIH, VA , NSF and several foundations.

Abstract: