The projects funded during the month of September include:
- Binding Site Characterization of a Novel Pyridazine-Derived Class of y-Secretase Modulators ($194,950)
This study by Steven Wagner, Ph.D. of University of California, San Diego will identify the critical sites of interaction between novel pyridazine-derives soluble gamma secretase modulators (SGSMs) and their molecular target, as well as provide valuable information toward fostering an improved understanding of the mechanism by which these therapeutically relevant small molecules affect the production of specific Abeta peptide variants without inhibiting the enzyme's activity. Despite the development of numerous potent SGSMs, the precise molecular target and mechanism of action of this clinically relevant pyridazine series remain unknown.
- Uncovering Determinants of Neuronal Vulnerability in Alzheimer's disease – Year 2 ($250,000)
This project, by Paul Greengard, Ph.D. of the Rockefeller University, will test whether three gene mutations are causative of the disease. The researchers will test if the candidate gene is involved in the pathogenesis of the disease by analyzing mice invalidated for this gene. They will also study three mutations and investigate how they interfere with the protein function. Finally, they want to elucidate the pathways the candidate gene is involved in. This gene is potentially a crucial novel actor of Alzheimer's disease pathogenesis that could explain specific vulnerability of certain neurons. Understanding its function and its molecular partners will yield new targets for the Alzheimer's disease research community, for generating drugs that would prevent vulnerable neurons from degenerating.
- Impact of Inflammasome Deactivation on Alzheimer's disease ($75,000)
This research, by Vishwa Deep Dixit, D.V.M., Ph.D. of Yale School of Medicine, which will be in interdisciplinary collaboration with the lab of Dr. Rudy Tanzi at Massachusetts General Hospital (MGH), emanates from the original findings that NLRP3 inflammasome activation in microglia controls age-related inflammation in the central nervous system (CNS) and that CD33-dependent inhibition of amyloid-beta uptake by microglia reduces IL-1beta to protect against AD. Inflammasome is a high molecular weight protein complex that assembles in the cytosol of microglia and myeloid-lineage cells upon encounter with 'damage-associated molecular patterns' such as amyloids, lipotoxic fatty acids or extracellular ATP derived from necrotic cells. Upon assembly, this causes caspase-1 dependent release of pro-inflammatory cytokines IL-1beta, IL-18 and a special form of cell death called pyroptosis1.
- Nanobodies to Cross the Blood-Brain Barrier ($150,000)
The purpose of this project, by Bart De Strooper, M.D., Ph.D. and Maarten Dewilde, Ph.D. of VIB Center for the Biology of Disease, KY Leuven, is to generate a universal tool that can transport drug molecules to the brain. The blood-brain barrier (BBB) is a vital barrier between the bloodstream and the brain. This barrier tightly controls which molecules can enter the brain. As a consequence of this barrier, the majority of currently available drugs can't enter the brain. Importantly, to treat Alzheimer's disease, drugs need to reach the brain.
- SORLA attenuates Aβ toxicity through interactions with EphA4 ($150,000)
This project, by Huaxi Xu, Ph.D. of Sanford Burnham Prebys Medical Discovery Institute, will confirm whether SORLA can limit toxic signals from EphA4 in response to Abeta (Aβ), and whether molecular strategies to enhance SORLA/EphA4 interactions can further protect neurons from synaptic damage from Aβ. Together, this study will potentially provide insight into a new pathway to protect neurons from Aβ damage, which may lead to strategies to improve cognition in patients with Alzheimer's disease.
Cure Alzheimer's Fund is a non-profit dedicated to funding the most promising research to prevent, slow or reverse Alzheimer's disease. Since its founding in 2004, Cure Alzheimer's Fund has contributed over $45 million to research, and its funded initiatives have been responsible for several key breakthroughs – including the groundbreaking "Alzheimer's in a Dish" study. Cure Alzheimer's Fund has received a score of 100 percent regarding its overall financial health from Charity Navigator and a four star rating from the organization five times. With 100 percent of funds raised going directly to research, Cure Alzheimer's has been able to support some of the best scientific minds in the field of Alzheimer's research. For more information, please visit Cure Alzheimer's Fund at www.curealz.org.
Logo - http://photos.prnewswire.com/prnh/20160525/372194LOGO
To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/cure-alzheimers-fund-issues-over-700000-in-research-grants-in-september-300344375.html
SOURCE Cure Alzheimer’s Fund