S. Aschmies
Princeton University
4 Papers
14 Citations
S. Aschmies is an academic researcher from Princeton University. The author has contributed to research in topics: Amyloid precursor protein & Biochemistry of Alzheimer's disease. The author has an hindex of 3, co-authored 4 publications.
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Papers
Enhanced clearance of Aβ in brain by sustaining the plasmin proteolysis cascade
Jacobsen Js,Thomas A. Comery,Robert Martone,Elokdah H,Crandall Dl,Oganesian A,S. Aschmies,Yolanda Kirksey,Gonzales C,J. Xu,Hua Zhou,Kevin Atchison,Erik Wagner,M.M. Zaleska,Das I,Robert L. Arias,Jonathan A. Bard,David Riddell,Stephen J. Gardell,Magid Abou-Gharbia,Albert J. Robichaud,Ronald L. Magolda,George P. Vlasuk,Bjornsson T,Peter H. Reinhart,Menelas N. Pangalos +25 more
TL;DR: PAI-1 inhibitors augment the activity of tPA and plasmin in hippocampus, significantly lower plasma and brain Aβ levels, restore long-term potentiation deficits in hippocampal slices from transgenic Aβ-producing mice, and reverse cognitive deficits in these mice.
142
(S)-N-(5-Chlorothiophene-2-sulfonyl)-β,β-diethylalaninol a Notch-1-sparing γ-secretase inhibitor
Derek C. Cole,Joseph Raymond Stock,Anthony F. Kreft,Madelene Antane,S. Aschmies,Kevin Atchison,David S. Casebier,Thomas A. Comery,George Diamantidis,John W. Ellingboe,Boyd L. Harrison,Yun Hu,Mei Jin,Dennis Kubrak,Peimin Lu,Charles William Mann,Robert Martone,William Jay Moore,Aram Oganesian,David Riddell,June Sonnenberg-Reines,Shaiu-Ching Sun,Erik Wagner,Zheng Wang,Kevin R. Woller,Zheng Xu,Hua Zhou,J. Steven Jacobsen +27 more
TL;DR: Researchers have identified the Notch-1-sparing (9.5-fold) gamma-secretase inhibitor (S)-N-(5-chlorothiophene-2-sulfonyl)-beta,beta-diethylalaninol 7.b.2 (Abeta(40/42) EC(50)=28 nM), which is efficacious in reduction of Abeta production in vivo.
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Synthesis and structure–activity relationship of a novel series of heterocyclic sulfonamide γ-secretase inhibitors
Jun Pu,Anthony F. Kreft,S. Aschmies,Kevin Atchison,Joshua D Berkowitz,Thomas J. Caggiano,Micheal Chlenov,George Diamantidis,Boyd L. Harrison,Yun Hu,Donna M. Huryn,J. Steven Jacobsen,Mei Jin,Kerri Lipinski,Peimin Lu,Robert Martone,Koi Michele Morris,June Sonnenberg-Reines,Dave R. Riddell,Joan E. Sabalski,Shaiu-Ching Sun,Erik Wagner,Yiqun Wang,Zheng Xu,Hua Zhou,Lynn Resnick +25 more
TL;DR: A novel series of heterocyclic sulfonamide gamma-secretase inhibitors that reduce beta-amyloid levels in cells is reported, and several examples of compounds demonstrate a higher propensity to inhibit the processing of amyloid precursor protein compared to Notch, an alternative gamma- secretase substrate.
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BACE1 is not the rate-limiting enzyme in Aβ production in the brains of APPswe transgenic mice: Pharmacological characterization of BACE1 using novel brain penetrant inhibitors.
David Riddell,Kevin Atchison,D. Yu,Jim Turner,E. Wang,Cathleen Gonzales,Helen K. Warwick,Kim Ji-In,Michael S. Malamas,Erik Wagner,S. Aschmies,Kristin Albinson,J. Erdel,Iwan Gunawan,Raquel Revilla-Sanchez,K. Takano,N. Warren,K. Fang,Jonathan A. Bard,Warren D. Hirst,Menelas N. Pangalos,Stephen J. Moss,Phillip Haydon,Albert J. Robichaud,Peter H. Reinhart +24 more
TL;DR: Bifunctional small molecules that are able to recruit other cellular proteins that have been shown to modulate A- beta aggregation and to genetically interact with the A-beta aggregation pathway can be used as chemical probes to address unanswered questions regarding the molecular mechanisms underlying the pathogenesis of AD.
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