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2010 Grants - Gauthier
CysC Restores the Flow of Autophagy to Counteract Alzheimer Pathogenesis
Sebastien Gauthier, Ph.D.
The Nathan S. Kline Institute for Psychiatric Research
Orangeburg, New York
2010 New Investigator Research Grant
Autophagy is a biochemical process by which small cell structures break down unwanted proteins and other cellular components. This process prevents cellular "waste products" from damaging or killing the cell. One such waste product is beta-amyloid, a protein fragment linked to brain cell damage and death in Alzheimer's disease. Research suggests that a protein called cystatin C may be used in the autophagic process. Cystatin C has been shown to bind to beta-amyloid and prevent it from accumulating into harmful clumps. Loss of cystatin C could lead to Alzheimer-related beta-amyloid clumping.
Based on earlier research with cultured brain cells, Sebastien Gauthier, Ph.D., and colleagues hypothesize that cystatin C activity is lessened by a signaling pathway—or series of molecular events—involving the protein called transforming growth factor-beta (TGF-beta). These events may also hinder the autophagic process in general. For their proposed study, the investigators will engineer brain cells with various levels of cystatin C and treat those cells with beta-amyloid. They will assess whether cystatin C works with the autophagic process to reduce beta-amyloid accumulation. They will then determine whether the TGF-beta signaling pathway lessens the ability of cystatin C to block amyloid clumping.
The results of this effort could shed new light on how autophagy and cystatin C combine to prevent brain cell damage in Alzheimer's disease. The work could also lead to Alzheimer therapies that target abnormalities in the autophagic process.