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Two Leading Alzheimer's Disease Researchers Recognized with MetLife Foundation Awards
Date:5/15/2013

>Dr. Li, who is a lab head in the Molecular Pharmacology and Chemistry Program at Memorial Sloan-Kettering Cancer Center, has made a number of seminal discoveries about the enzyme gamma-secretase and its role in the pathology of Alzheimer’s disease.

In a 2000 publication in Nature, his team provided the first compelling biochemical evidence that gamma-secretase activity is triggered by subunits within this complex called presenilin. Presenilins, when mutated, can lead to Alzheimer’s disease.

In 2010, his lab reconstituted gamma-secretase and provided proof that presenilin contains the active site for gamma-secretase. This finding provided a unique platform for further study, which is now being done by a number of research teams, of the structure and function of gamma-secretase at both the molecular and atomic levels. Dr. Li’s discovery provides further proof that gamma-secretase is a potential target for the development of Alzheimer’s treatments.

Dr. Li’s primary research focus is now on modulating gamma-secretase activity in order to change the processing of amyloid precursor protein (APP), a protein implicated in the development of Alzheimer’s disease, and translating this knowledge into targeted therapies.

As director of the Gladstone Institute of Neurological Disease, Dr. Mucke and his team have made a number of significant discoveries on the mechanisms underlying Alzheimer’s disease, and have identified novel therapeutic strategies for blocking these mechanisms. His lab showed that the activities of the proteins amyloid-beta, apoE4 and tau, all of which are known to be involved in Alzheimer’s disease, can disturb communication among brain cells. Dr. Mucke’s team also discovered that the interactions of these proteins play an early role in disrupting the brain’s neural networks. In addition, Dr. Mucke found that some of the over-excitation of neurons known to be an early characteristic of Alzheimer’s disease results from
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