William Mobley, M.D., Ph.D.

Distinguished Professor and Chair of the Department of Neurosciences at University of California at San Diego

Executive Director of UCSD's Down Syndrome Center for Research and Treatment

Dr. Mobley has a distinguished record of academic achievement and is considered one of the most prominent academic neurologists in the US. He has an international reputation for his research on degenerative disease of the central nervous system as well as being a leader in translational medicine, bridging clinical and basic science.

Dr. Mobley came to UCSD in June 2009 from Stanford University in Palo Alto, Calif., where he served as the John E. Cahill Family Professor in the Department of Neurology and Neurological Sciences and was the founding director of the Neuroscience Institute. Dr. Mobley is the recipient of both the Zenith Award and the Temple Award from the Alzheimer’s Association and was chosen to receive the Cotzias Award of the American Academy of Neurology in 2004. Dr. Mobley is Past President of the Association of University Professors of Neurology, of the Professors of Child Neurology, and of the International Society for Developmental Neuroscience.  He is a Fellow of the Royal College of Physicians and in 2006 was named a Fellow of the American Association for the Advancement of Science.

Funded Research

Project Description Researchers Funding
GABAergic inhibitory efficiency and adult neurogenesis in the hippocampus of aged Ts65Dn mice, a model of ‘Alzheimer’s disease in Down syndrome’, after chronic treatment with the monoacylglycerol lipase inhibitor JZL184

Recently we observed that chronic suppression of monoacylglycerol lipase with the selective blocker JZL184 increased brain levels of endocannabinoid 2-arachidonoil glycerol (2-AG), restored long-term potentiation, improved cognition, and reduced brain levels of Aβ40 and Aβ42 in aged Ts65Dn mice, a model of ‘Alzheimer’s disease in Down syndrome’ (ADDS). In this proposal, we plan to examine the mechanisms responsible for the restoration of cognition and synaptic plasticity in the ADDS model mice.

Effects of Inhibitors of Monoacylglycerol Lipase on Behavior and Synaptic Plasticity of Ts65Dn Mice, a Genetic Model of Down Syndrome

Alzheimer’s Disease (AD) is caused by a complex interplay between genetic, epigenetic and environmental factors. Mutations in three genes, amyloid precursor protein (APP), presenilin (PS)‐1 and (PS)‐2 account for early onset autosomal dominant AD (Bertram and Tanzi, 2012). People with Down syndrome (DS) carry and extra copy of chromosome 21, which contains a copy of the APP gene. As a result, by the 4th decade all people with DS exhibit the AD type neuropathology and most go on to show dementia by age 60. Thus, DS can be regarded as a valid and robust model of AD.

Design, Synthesis and Characterization of Novel and Potent Gamma Secretase Modulators: Physiochemical and Pharmacokinetic Properties

During the past year, our laboratory at UCSD (Wagner laboratory), in close collaboration with the Tanzi laboratory at MGH, discovered, synthesized and characterized (in vitro) a novel series of molecules able to potently prevent the formation of what is currently thought to be the pathogenic culprit of Alzheimer’s disease (AD).


Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.
Steven L. Wagner, Kevin D. Rynearson, Steven K. Duddy, Can Zhang, Phuong D. Nguyen, Ann Becker, Uyen Vo, Deborah Masliah, Louise Monte, Justin B. Klee, Corinne M. Echmalian, Weiming Xia, Luisa Quinti, Graham Johnson, Jiunn H. Lin, Doo Y. Kim, William C. Mobley, Robert A. Rissman, Rudolph E. Tanzi, Pharmacological and Toxicological Properties of the Potent Oral gamma-Secretase Modulator BPN-15606, Journal Of Pharmacology And Experimental Therapeutics, 362(1), Jul 2017, 31-44
Pavel V. Belichenko, Alexander M. Kleschevnikov, Ann Becker, Grant E. Wagner, Larisa V. Lysenko, Y. Eugene Yu, and William C. Mobley, Down Syndrome Cognitive Phenotypes Modeled in Mice Trisomic for All HSA 21 Homologues, PLoS One, 10(7), July 2015