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2014 Grants - Dobrowolski
Dysregulation of Molecular Clearance Pathways in Alzheimer’s Disease
Radoslaw Dobrowolski, Ph.D.
Rutgers, The State University of New Jersey — Newark Campus
Newark, New Jersey
2014 New Investigator Research Grant
All cells contain mechanisms for removing waste products such as old proteins and cellular debris. One such system is the lysosomal system. In brain cells, a change that occurs in the earliest stages of Alzheimer’s disease is malfunction of the lysosomal system, which may accelerate the accumulation of the protein fragment beta-amyloid in the brain. When beta-amyloid accumulates in the brain, it forms clumps known as amyloid plaques, a characteristic feature of Alzheimer’s disease.
Radoslaw Dobrowolski, Ph.D., and colleagues have found evidence that malfunction of a particular molecular pathway important for regulating the lysosomal system affects the accumulation of beta-amyloid. This signaling pathway involves a complex of proteins known as mTOR (mammalian target of rapamycin) and another protein known as TFEB (transcription factor EB). The researchers have proposed a series of studies to determine how the mTOR/TFEB pathway may affect the production and accumulation of beta-amyloid in nerve cells grown in laboratory dishes.
Dr. Dobrowolski and colleagues also plan to study how mTOR/TFEB signaling controls the activity of proteins known to alter tau; tau is the major component of neurofibrillary tangles, another characteristic feature of Alzheimer’s disease. These studies may help scientists understand the molecular mechanisms occurring in very early stages of Alzheimer’s disease, including the processes leading to the accumulation of amyloid plaques and formation of neurofibrillary tangles. A better understanding of these processes may contribute to the future development of novel treatments for Alzheimer’s disease.