Neurodegenerative Diseases

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Dr. Yokel's research focuses on metals, particularly those that contribute to neurodegenerative disorders. Recently completed work addressed the influx and efflux of manganese across the blood-brain barrier and mediating mechanisms, and the oral bioavailability of aluminum, a suggested contributor to Alzheimer’s disease. Another ongoing funded project is assessing the physico-chemical properties of nanoscale ceria that influence its distribution into the brain and effects on the blood-brain barrier and brain. Engineered nanoscale ceria is being studied as a model engineered nanomaterial and because it is in commercial use as a diesel fuel additive, resulting in its release into the environment, with unknown potential effects.  
Dr. Kasarskis is an active clinician and an ALS expert neurologist focused on movement disorders, specifically Amyotrophic Lateral Sclerosis (ALS).  ALS is a human neurodegenerative disease that is multifactorial in its etiology, with a combination of genetic predisposition and an inciting set of environmental factors.  While some cases of ALS (~10%) are clearly genetic with an autosomal dominant pattern of inheritance linked to mutations in certain genes (SOD1, TDP43, FUS/TLS, and others to be identified), the majority of cases are sporadic.  Several potential environmental factors have been linked to ALS, including agricultural chemicals, lead exposure, diet, smoking, and military service.  Dr. Kasarskis is leading a team of experts in epidemiology, genetics, and biostatistics to develop a combined regional/state based ALS registry comprising Kentucky and Tennessee as a means of developing a National ALS Registry.
Dr. Gash's research focuses on neurodegenerative changes in the nonhuman primate and human brain, including analyzing the role of environmental neurotoxins in initiating and/or exacerbating disease processes.  Dr. Gash is specifically interested in developing and testing new therapeutic approaches to effectively deliver drugs to the brain to slow down and even reverse degenerative changes.  Dr. Gash’s current studies, funded by both NIH and pharmaceutical companies, involve (1) developing GDNF-like trophic peptides for treating Parkinson’s disease, and (2) evaluating siRNA suppression of huntingtin expression in the nonhuman primate striatum as a possible treatment for Huntington’s disease.  These studies are multidisciplinary, including conducting extensive behavioral testing, experimental neurosurgery, MRI brain scans, in vivo microdialysis in awake animals, and quantitative morphological assessment of neural restoration.
Dr. Zhu utilizes proteomic, biochemical and cell biology approaches to study neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease).  Mutations in the antioxidant protein copper-zinc superoxide dismutase (SOD1) have been found in a subset of familial ALS patients. Dr. Zhu’s research is focused on elucidating the neurotoxicity of the mutant variants of SOD1. The hypothesis to be tested in his lab is that the mutant SOD1 protein can form aggregates associated with mitochondria and disrupt mitochondrial function. Recent results in his laboratory also suggest that mutant SOD1 can interfere with axonal transport in neurons, the process that is critical to mitochondrial dynamics (trafficking, fission, and fusion). Interference with axonal transport thus can lead to abnormal mitochondria morphology and function. This hypothesis is currently being tested by a combination of genetic, biochemical and cell biology approaches.
Dr. Slevin is an active clinician who also conducts basic, translational and clinical research with collaborators across the UK Medical Center.  His translational and clinical research interests focus on the etiology, pathophysiology and treatment of movement disorders, particularly Parkinson’s disease (PD).  In collaboration with Dr. Don Gash, and others, Dr. Slevin is systematically evaluating a group of subjects who experienced chronic occupational exposure to trichloroethylene (TCE); some of these individuals have developed PD and others have shown suggestive signs and symptoms although they do not yet meet criteria for diagnosis.