William J. Netzer, PhD. Research Associate, Laboratory of Molecular and Cellular Neuroscience and The Fisher Center for Alzheimer’s Disease Research at The Rockefeller University.
Dr. Netzer received his PhD in 1997 at the Cornell University School of Medical Sciences and began post doctoral study in the laboratory of Paul Greengard at The Rockefeller University in 1999. He was promoted to Research Associate in 2004. Dr. Netzer conducts research on Alzheimer’s disease in an attempt to elucidate cellular and biochemical mechanisms that regulate production of beta-amyloid, which is believed to be the primary cause of Alzheimer’s disease. His long-term goal is to discover molecules within brain cells that would act as therapeutic targets for drugs aimed at treating Alzheimer’s disease. In 2000, Dr. Netzer discovered that gamma-secretase, one of the principal enzymes necessary for beta-amyloid production, is dependent on the energy related molecule, ATP. Dr. Netzer took advantage of this finding and in 2003 discovered that the anti-cancer drug, Gleevec (which was an ATP blocker) inhibits production of beta-amyloid. Gleevec is not suitable for the treatment of Alzheimer’s disease because it is unable to penetrate the blood-brain-barrier. More recently, Dr. Netzer discovered that a prototype drug related to Gleevec is able to penetrate the blood-brain-barrier and, like Gleevec, inhibits beta-amyloid production. His goal is to use this molecule as a basis for discovering new beta-amyloid inhibiting drugs.
Dr. Netzer has worked with other scientists in the Greengard laboratory to identify the molecule within brain cells that acts as Gleevec’s target and is responsible for Gleevec’s ability to inhibit beta-amyloid production. Recently, Fisher scientists (a team that included Dr. Netzer) discovered that the Gleevec target responsible for beta-amyloid production is a protein, now referred to as gSAP (for gamma-secretase activating protein). This discovery has provided an understanding of how gamma-secretase is regaled to control beta-amyloid production in the brain and in Alzheimer’s disease. gSAP is currently a major pharmaceutical target for the discovery of a new class of drugs for treating Alzheimer’s disease.
Dr. Netzer has also conducted research on Down syndrome, which bears similarities to Alzheimer’s disease in that beta-amyloid levels are raised in the Down syndrome brain. Dr. Netzer recently demonstrated that cognitive deficits displayed by a mouse model of Down syndrome can be corrected by inhibiting the production of beta-amyloid. This suggests that mental retardation in Down syndrome children might be treatable by beta-amyloid lowering drugs.