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2016 Grants - Velazquez
Pim1 Inhibition as a Therapeutic Strategy for Alzheimer’s Disease
Ramon Velazquez, Ph.D.
Arizona State University
2016 Alzheimer’s Association Research Fellowship to Promote Diversity (AARF-D)
Can the regulation of a molecule involved in producing and degrading proteins lead to a novel Alzheimer’s treatment?
Alzheimer’s disease is characterized by the accumulation of beta-amyloid protein fragments into “plaques” and abnormal tau protein into “tangles” in the brain. These harmful clumps of proteins can damage brain cells and promote memory loss and other forms of cognitive decline. Although it is not yet clear what triggers the accumulation of beta-amyloid and tau, research indicates that the brain’s ability to produce new proteins and degrade unwanted ones becomes impaired during Alzheimer’s disease.
In initial studies using Alzheimer’s-like mice, Ramon Velazquez, Ph.D., and colleagues found that a protein called Pim1 may be involved in molecular pathways that lead to the clumping of harmful beta-amyloid and tau in the brain. Dr. Velazquez and colleagues treated the mice with a compound that could inhibit Pim1 and found that it reduced beta-amyloid and tau levels in the mice and improved their cognitive function. However, the treatment also led to harmful side effects on the spleen and other organs in the animals. More research is needed to determine if a method to selectively reduce Pim1 only in the brain can be devised to increase safety and effectiveness.
For their current grant, Dr. Velazquez and colleagues will develop a “nanoparticle” delivery system that should help the Pim1 inhibitor act only on the brain while protecting the rest of the body from unwanted side effects. The researchers will determine whether their refined therapy can reduce beta-amyloid and tau levels in the brain without promoting harmful side effects. The investigators will administer the treatment to Alzheimer’s-like mice at different stages of the disease to determine if the drug can prevent or reverse nerve cell loss and memory problems.
If successful, this effort could help lay the foundation for future human clinical trials to determine if the nanoparticle delivery of Pim1 inhibitors is a safe and effective treatment to prevent or slow Alzheimer’s disease.