Yi Chen
Pfizer
8 Papers
Yi Chen is an academic researcher from Pfizer. The author has contributed to research in topics: Neuroprotection & LRRK2. The author has an hindex of 7, co-authored 8 publications.
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Papers
Pathogenic LRRK2 mutations, through increased kinase activity, produce enlarged lysosomes with reduced degradative capacity and increase ATP13A2 expression
Anastasia G. Henry,Soheil Aghamohammadzadeh,Harry Samaroo,Yi Chen,Kewa Mou,Elie Needle,Warren D. Hirst +6 more
TL;DR: It is demonstrated that L RRK2 regulates lysosome size, number and function in astrocytes, which endogenously express high levels of LRRK2, and that blocking LRRk2's kinase activity, with the potent and selective inhibitor PF-06447475, rescues the observed defects in lysOSomal morphology and function.
Leucine-rich Repeat Kinase 2 (LRRK2) Pharmacological Inhibition Abates α-Synuclein Gene-induced Neurodegeneration
João Paulo Lima Daher,Hisham Abdelmotilib,Xianzhen Hu,Laura A. Volpicelli-Daley,Mark S. Moehle,Kyle B. Fraser,Elie Needle,Yi Chen,Stefanus J. Steyn,Paul Galatsis,Warren D. Hirst,Andrew B. West +11 more
TL;DR: It is demonstrated that pharmacological inhibition of LRRK2 is well tolerated for a 4-week period of time in rats and can counteract dopaminergic neurodegeneration caused by acute α-synuclein overexpression.
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Behavioral characterization of A53T mice reveals early and late stage deficits related to Parkinson's disease.
Katrina L. Paumier,Stacey J. Sukoff Rizzo,Zdenek Berger,Yi Chen,Cathleen Gonzales,Edward Kaftan,Li Li,Susan M. Lotarski,Michael Monaghan,Wei Shen,Polina Stolyar,Dmytro Vasilyev,Margaret M. Zaleska,Warren D. Hirst,John Dunlop +14 more
TL;DR: Results from open field and rotarod tests show A53T mice develop age-dependent changes in locomotor activity and reduced anxiety-like behavior, and digigait analysis shows these mice develop an abnormal gait by 12 months of age, which may provide useful endpoints for assessing novel therapeutic interventions for PD.
Discovery and preclinical profiling of 3-[4-(morpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile (PF-06447475), a highly potent, selective, brain penetrant, and in vivo active LRRK2 kinase inhibitor.
Jaclyn Louise Henderson,Bethany L. Kormos,Matthew Merrill Hayward,Karen J. Coffman,Jayasankar Jasti,Ravi G. Kurumbail,Travis T. Wager,Patrick Robert Verhoest,G. Stephen Noell,Yi Chen,Elie Needle,Zdenek Berger,Stefanus J. Steyn,Christopher Houle,Warren D. Hirst,Paul Galatsis +15 more
TL;DR: The discovery and optimization of a novel series of potent LRRK2 inhibitors are disclosed, focusing on improving kinome selectivity using a surrogate crystallography approach, which resulted in the identification of 14 (PF-06447475), a highly potent, brain penetrant and selective L RRK2 inhibitor which has been further profiled in in vivo safety and pharmacodynamic studies.
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Binding of rapamycin analogs to calcium channels and FKBP52 contributes to their neuroprotective activities
Benfang Ruan,Kevin Pong,Flora Jow,Mark R. Bowlby,Robert A. Crozier,Danni Liu,Shi Liang,Yi Chen,Mary Lynn T. Mercado,Xidong Feng,Frann Bennett,David von Schack,Leonard A. McDonald,Margaret M. Zaleska,Andrew R. Wood,Peter H. Reinhart,Ronald L. Magolda,Jerauld S. Skotnicki,Menelas N. Pangalos,Frank E. Koehn,Guy T. Carter,Magid Abou-Gharbia,Edmund I. Graziani +22 more
TL;DR: Modification at the mammalian target of rapamycin (mTOR) binding region yields immunophilin ligands, WYE-592 and ILS-920, with potent neurotrophic activities in cortical neuronal cultures, efficacy in a rodent model for ischemic stroke, and significantly reduced immunosuppressive activity.
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