We are interested in elucidating the biological basis of neurodegeneration. There is now a basic understanding of the clinical, pathological, and some genetic features of many neurodegenerative disorders. Lacking, however, is a satisfactory biochemical explanation for the progressive deterioration of the structural and functional integrity in the brains afflicted with these egregious illnesses. Aiming to fill this knowledge gap, we use in vivo, in vitro, and structural tools to focus on several areas related to degeneration, protection, and regeneration of the central nervous system. In particular, we are interested in mapping the molecular circuits of neurodegenerative diseases, including Alzheimer disease and frontotemporal dementia. Moreover, we are interested in a mechanistic and structural understanding of the "demented" molecular machines, such as the gamma-secretase complex.
RESEARCH INTERESTS
Alzheimer Disease
Frontotemporal Lobar Degeneration
The Gamma-Secretase Complex
RECENT PUBLICATIONS
Lee SF, Shah S, Yu C, Wigley WC, Li H, Lim M, Pedersen K, Han W, Thomas P, Lundkvist J, Hao YH, Yu G, "A conserved GXXXG motif in APH-1 is critical for assembly and activity of the gamma-secretase complex" J Biol Chem, 279:4144-52, 2004
Shah S, Lee S, Tabuchi K, Hao Y, Yu C, LaPlant Q, Ball H, Dann C, Sudhof T, and Yu G, "Nicastrin Functions As A Gamma-Secretase-Substrate Receptor" Cell, 122:435-447, 2005
Shah, S and Yu G, "SorLA: Sorting Out APP." Mol. Interv., 6:74-76, 2006
Tu H, Nelson O, Bezprozvanny A, Wang Z, Lee SF, Hao YH, Serneels L, De Strooper B, Yu G, Bezprozvanny I, "Presenilins Form ER Ca(2+) Leak Channels, a Function Disrupted by Familial Alzheimer’s Disease-Linked Mutations" Cell, 126:981-993, 2006
SIGNIFICANT PUBLICATIONS
Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, Song YQ, Rogaeva et al., "Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing" Nature, 407:48-54, 2000
Shah S, Lee S, Tabuchi K, Hao Y, Yu C, LaPlant Q, Ball H, Dann C, Sudhof T, and Yu G, "Nicastrin Functions As A Gamma-Secretase-Substrate Receptor" Cell, 122:435-447, August 2005
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