Gregory Brewer, PhD

Professor, MIND Institute, Center for Neuroscience of Learning and Memory and Dept. Biomedical Engineering, Univ. California, Irvine

Brewer began studies of bioenergetics in 1972 with studies of NADH and teaching mass spec at MIT while a postdoc.  After broad training in membrane biochemistry, microbial genetics and membrane biophysics, his past 25 years have been devoted to aging brain research.  For these studies, he developed two critical technologies: 1) serum-free Neurobasal-B27 medium and 2) the ability to culture adult neurons of any age (see C1,2 below).  The adult culture technology has enabled aging studies of neurons throughout the age-span to identify age-related deficits in neuron glucose uptake, improvements in brain mitochondrial function with redox agents and detailed analyses of whole neuron metabolism.  Specific flux-control dissection of the electron transport chain found brain age-related loss of function due to NADH substrate limitations at complex I and cytochrome C as well as enzymatic deficits at complex IV.  In 2013, Brewer moved to UC Irvine where he enjoys interactions with Michael Yassa for functional brain imaging in the elderly and Charlie Glabe for amyloid structure.  His prior grant on “Mitoenergetic Failure in Brain Aging” (RO1 AG032431) produced 16 publications (a, b most relevant are listed).  Recent funding focused on redox bioenergetic deficits, breaking new ground in aging brain and in AD mouse models (RF1-AG058218-01, “Age-related metabolic alterations in amyloid processing in AD” yielded 7 publications; c, d most relevant). Most significantly, these age-related deficits could be rapidly reversed by simple treatment with estrogen for 2 days or nicotinamide overnight to provide more NAD/NADH implicating epigenetic involvement. Here we begin a new collaboration with an epigenetics expert in our department, Tim Downing for Aim 2. Systematic studies of primary neurons in culture have led to the Brewer’s findings in age-related changes in brain metabolism of amyloid that suggest a translational therapeutic approach.