Research Overview
Alzheimer's Disease
Alzheimer's disease is a neurodegenerative disease which was the 7th leading cause of death in the United States in 2004. Alzheimer's is a major focus of biomedical research, and there is still much to be learned about the cellular events that lead to this devastating disease. An understanding of the molecular mechanisms of the disease will lead to new targets for drug discovery.
Protein Processing
Almost every aspect of survival and reproduction in living cells is accomplished, at the molecular level, by interactions between proteins, or between proteins and other molecules...
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Research Description
Research Area: Neurodegenerative Diseases
Research Specialties: Alzheimer's disease. presenilin-protein interactions. cell cycle regulation, calcium-binding proteins, ubiquitin-proteasome system
The research focus of the laboratory is geared toward studying the mechanisms and treatments of Alzheimer's disease (AD) and related disorders. Our studies are directed toward two general areas: the role of presenilins (PS) and associated proteins in AD, and the role of protein misfolding and the ubiquitin-proteasome system in neurodegenerative disorders.
Role of Presenilins in Alzheimer's disease
The majority of familial cases of AD (FAD) are due to inheritance of mutations in the genes encoding the two highly homologous proteins, PS1 and PS2. Our studies focus on the function of PS proteins and on how AD-associated mutations in these proteins cause disease. A primary focus of these studies is directed toward two PS-associated proteins, ubiquilin and calmyrin, which we have found modulate PS functions. In earlier studies we showed...
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Representative Publications
Janicki, S., and M.J. Monteiro. 1997. Increased apoptosis arising from increased expression of the Alzheimer's disease-associated presenilin-2 mutation (N141I). J Cell Biol. 139:485-95.
Janicki, S.M., and M.J. Monteiro. 1999. Presenilin overexpression arrests cells in the G1 phase of the cell cycle. Arrest potentiated by the Alzheimer's disease PS2(N141I)mutant. Am J Pathol. 155:135-44.
Stabler, S.M., L.L. Ostrowski, S.M. Janicki, and M.J. Monteiro. 1999. A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer's disease presenilin 2 protein. J Cell Biol. 145:1277-92.
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