To view an abstract, select an author from the vertical list on the left side.
2008 Grants - Yang
Rescue Autophagic-Lysosomal Protein Degradation to Reverse Amyloid Pathology
Dun-Sheng Yang, Ph.D.
Nathan S. Kline Institute for Psychiatric Research
Orangeburg, New York
2008 Investigator-Initiated Research Grant
Lysosomes are small structures inside all cells that specialize in breaking down expended proteins and other spent cellular components. The autophagic-lysosomal pathway is one biochemical pathway by which lysosomes perform this task, preventing cellular "waste products" from accumulating and damaging or killing the cell. Malfunction of lysosomes in general, and the autophagic-lysosomal pathway in particular, have been implicated in several neurodegenerative diseases, including Alzheimer's disease.
Dun-Sheng Yang, Ph.D., and colleagues have found evidence that late steps in the autophagic-lysosomal pathway are defective in some animal models of Alzheimer's disease. This defect causes partially degraded proteins to accu-mulate inside of cells. One consequence is the accumulation of beta-amyloid, a protein fragment that aggregates to form amyloid plaque, a key feature of Alzheimer pathology.
Dr. Yang and colleagues have also found early evidence that defective steps in the authophagic-lysosomal pathway may be repaired, thereby reducing the accumulation of beta-amyloid. They have planned an additional series of experiments to test this idea.
The researchers will use two mouse models of Alzheimer's disease that also exhibit defects in the authophagic-lysosomal pathway. They will use genetic engineering techniques to restore or enhance the function of this pathway and then test how those changes affect the accumulation of amyloid plaque and neurodegeneration. These studies could help to identify a key step leading to the development of Alzheimer pathology, as well as potential approaches for treatment.