NADAM 2017
Research Grants - 2016


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Research Grants 2016


To view an abstract, select an author from the vertical list on the left.

2016 Grants - Pearn

Small Molecules to Normalize Early Endosome Structure and Function in Alzheimer’s Disease

Matthew Pearn, M.D.
University of California, San Diego
La Jolla, California

2016 Collaboration 4 Cure (C4C)

Can a novel compound help prevent dysfunction of nerve cell transport systems in Alzheimer’s disease?

Background
Nerve cells internalize and transport nutrients, small molecules, and proteins through a process called “endocytosis.” During this process, the materials are packaged into “endosomes” which can then carry their cargo into the cell. These endosomes resemble small fluid-filled containment vessels. Endosomes are critical to the normal function of nerve cells, but in Alzheimer’s disease they become enlarged and abnormally accumulate in the brain. Researchers hypothesize that endosome dysfunction may contribute to brain changes associated with Alzheimer’s disease.

Accumulation of enlarged endosomes with a protein called Rab5 on their surface is a hallmark of early abnormal brain changes associated with Alzheimer’s disease. As endosomes begin to accumulate in nerve cells of individuals with Alzheimer’s, Rab5 becomes highly active causing dysfunction of the transport mechanism of these endosomes. Drug-like compounds that target Rab5 activity may be able to help prevent endosome dysfunction in the earliest stages of Alzheimer’s disease.

Research Plan
Matthew Pearn, M.D., and colleagues have developed a plan to identify compounds that may normalize the size and number of endosomes in Alzheimer’s disease. Endosomes with Rab5 activated on their membranes can be counted and measured under a microscope. The researchers will mimic Alzheimer’s disease in nerve cells grown in a laboratory dish to establish a baseline measurement of endosome appearance and quantity. They will then screen thousands of compounds to determine their effects on the size and number of endosomes in the nerve cells. The most promising compounds will be further tested for their effects on nerve cell function and survival.

Impact
Early detection and treatment of Alzheimer’s disease could help preserve the complex network of nerve cells in the brain. This study offers an opportunity to identify drug targets that could help normalize endosome function and slow the disease in its earliest stages.


Alzheimer's Association International Conference | July 16-20, 2017, London, England

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