Alzheimer’s disease is a devastating disorder for which there is no cure available at present. It is clear from previous studies that production and deposition of beta-amyloid peptides is causally linked to Alzheimer’s disease. Understanding the molecular mechanisms involved in the production of betaamyloid peptide is central to Alzheimer’s disease research. Several Alzheimer’s disease therapeutics being developed aim at reducing beta-amyloid production or deposition in brain, including beta-amyloid vaccination and pharmacological inhibition of y-secretase. Although vaccination studies in transgenic mouse models were extremely promising, human vaccination trials have met with unfortunate consequences of brain inflammation, including death of one patient. On the other hand, studies in animal models showed that inhibition of y-secretase using highly selective inhibitors still led to adverse effects related to inhibition of y-secretase processing of Notch, such as gross enlargement of spleen, skin inflammation, abnormalities in hematopoiesis etc.
Dr. Thinakaran and his lab believe that their studies will provide proof of principle for a novel strategy to reduce beta-amyloid production in the brain without adversely affecting Notch processing. Their preliminary studies in cultured cells strongly support this hypothesis, and they plan to use funding from their BRF seed grant to extend their studies in transgenic mice, as a logical step towards establishing lipid modification of y-secretase as a potential target to combat Alzheimer’s disease betaamyloid production and deposition.

Other Grants

Sarah C. Goetz, Ph.D., Duke University
Uncovering a Novel Role for Primary Cilia in Eph/Ephrin Signaling in Neurons
2022 Seed GrantSarah C. Goetz, Ph.D. Duke University Women’s Council Seed Grant Primary cilia are tiny projections from cells that function like an antenna- they receive and may also send…
Erin M. Gibson, Ph.D., Stanford University
Circadian Regulation of Oligodendroglial Senescence and Metabolomics in Aging
2022 Seed GrantErin M. Gibson, Ph.D.Stanford University The brain consists of two main classes of cells, neurons and glia. Glia make-up more than half of the cells in the brain…
Yvette Fisher, Ph.D., University of California, Berkeley
Dynamic Modulation of Synaptic Plasticity During Spatial Exploration
2022 Seed GrantYvette Fisher, Ph.D.University of California, Berkeley The Virginia (Ginny) & Roger Carlson Seed Grant Cognitive flexibility is critical for appropriately adjusting thoughts and behaviors to meet changing demands…
Byoung Il Bae, Ph.D., University of Connecticut
Unique Vulnerability of Developing Human Cerebral Cortex to Loss of Centrosomal Protein
2022 Seed GrantByoung Il Bae, Ph.D.University of Connecticut Carl & Marilynn Thoma Foundation Seed Grant The cerebral cortex is the largest and outermost part of the human brain. It is…