Easton Center - Pilot Project 13.1: Examination of a Novel Drug Candidate for Alzheimer’s Disease in a Translational Animal Model

Publications

  • S Sinha, DHJ Lopes, Z Du, ES Pang, A Shanmugam, A Lomakin, P Talbiersky, A Tennstaedt, K McDaniel, R Bakshi, P-Y Kuo, M Ehrmann, GB Benedek, JA Loo, F-G Klärner, T Schrader, C Wang, and G Bitan. Lysine-specific molecular tweezers are broad-spectrum inhibitor of aggregation and toxicity of amyloid proteins. J. Am. Chem. Soc2011; 133(42): 16958–16969.
  • S Sinha, Z Du, P Maiti, F-G Klärner, T Schrader, C Wang, and G Bitan. Comparison of Three Amyloid Assembly Inhibitors: The Sugar scyllo-Inositol, the Polyphenol Epigallocatechin Gallate, and the Molecular Tweezer CLR01. ACS Chem. Neurosci2012; 3(6): 451-458.
  • S Sinha, DHJ Lopes, and G Bitan. A Key Role for Lysine Residues in Amyloid β-Protein Folding, Assembly, and Toxicity. ACS Chem. Neurosci2012; 3(6): 473-481.
  • T Liu and G Bitan. Modulating Self-Assembly of Amyloidogenic Proteins as a Therapeutic Approach for Neurodegenerative Diseases: Strategies and Mechanisms. ChemMedChem2012; 7: 359-374.
  • A Attar, C Ripoli, E Riccardi, P Maiti, DD Li Puma, T Liu, J Hayes, MR Jones, K Lichti-Kaiser, F Yang, GD Gale, C-h Tseng, M Tan, C-W Xie, JL Straudinger, F-G Klärner, T Schrader, SA Frautschy, C Grassi and G Bitan. Protection of primary neurons and mouse brain from Alzheimer’s pathology by molecular tweezers. Brain2012; 135(Pt 12): 3735-3748.
  • A Attar, F Rahimi, and G Bitan. Modulators of amyloid protein aggregation and toxicity: EGCG and CLR01. Translational Neuroscience2013; 4(4): 385-409.
  • A Attar, W-TC Chan, F-G Klärner, T Schrader, and G Bitan. Safety and pharmacological characterization of the molecular tweezer CLR01 – a broad-spectrum inhibitor of amyloid proteins’ toxicity. BMC Pharm. Tox2014; 15(23): doi:10.1186/2050-6511-15-23.
  • A Attar and G Bitan. Disrupting self-assembly and toxicity of amyloidogenic protein oligomers by ” molecular tweezers” – from the test tube to animal models, Curr. Pharm. Des. 2014; 20: 2469-2483.
  • X Zheng, D-Y Liu, F-G Klärner, T Schrader, G Bitan, and MT Bowers. Amyloid β-protein Assembly: The Effect of Molecular Tweezer CLR01 and CLR03. J. Phys. Chem. B2015; 119: 4831-4841.
  • R Malishev, S Nandi, S Kolusheva, Y Levi-Kalisman, F-G Klärner, T Schrader, G Bitan*, and R Jelinek*, Toxicity inhibitors protect lipid membranes from disruption by Aβ42, ACS Chem. Neurosci. 2015; 6: 1860-1869.
  • T Schrader, G Bitan, and F-G Klärner, Molecular Tweezers for Lysine and Arginine – Powerful Inhibitors of Pathologic Protein Aggregation, Chem. Commun. 2016; 52: 11318-11334.
  • R Malik, J Di, G Nair, A Attar, K Taylor, E Teng, F-G Klärner, T Schrader, and G Bitan, Using molecular tweezers to remodel abnormal protein self-assembly and inhibit the toxicity of amyloidogenic proteins.Methods Mol. Biol. 2018, 1777: 369-386.
  • M Nshanian, C Lantz, P Wongkongkathep, T Schrader, F-G Klärner, A Blümke, C Despres, M Ehrmann, C Smet-Nocca, G Bitan, and JA Loo,  Native Top-Down Mass Spectrometry and Ion Mobility Spectrometry of the Interaction of Tau Protein with a Molecular Tweezer Assembly Modulator J. Am. Soc. Mass Spectrom2018,DOI: 10.1007/s13361-018-2027-6.
  • C Despres, J Di, F-X Cantrelle, Z Li, I Huvent, B Chambraud, J Zhao, J Chen, S Chen, G Lippens, F Zhang, R Linhardt, C Wang, F-G Klärner, T Schrader, I Landrieu, G Bitan, and Caroline Smet-Nocca (2019) Major differences between the self-assembly and seeding behavior of heparin-induced- and in-vitro-phosphorylated tau and their modulation by potential inhibitors. ACS Chem. Biol., 14: 1363-1379.
  • I Hadrovic, P Rebmann, F-G Klärner, G Bitan, and T Schrader (2019) Molecular Lysine Tweezers Counteract Aberrant Protein Aggregation. Front. Chem. 7: 657.
  • AJ Mason, I Hurst, R Malik, I Siddique, I Solomonov, I Sagi, F-G Klärner, T Schrader, and G Bitan (2020) Different Inhibitors of Aβ42-Induced Toxicity Have Distinct Metal-Ion Dependency. ACS Chem. Neurosci. 11: 2243–2255.
  • J Di, I Siddique, Z Li, G Malki, S Hornung, S Dutta, I Hurst, E Ishaaya, A Wang, S Tu, A Boghos, I Ericsson, F-G Klärner, T Schrader, and G Bitan (2021) The molecular tweezer CLR01 improves behavioral deficits and reduces tau pathology in P301S-tau transgenic mice. Alz. Res. Ther., 13: 6.

Grants

  • 2011-2012 Cure Alzheimer’s Fund “Molecular tweezers – novel inhibitors of amyloidogenic proteins and promising drug candidates for Alzheimer’s disease”
  • 2012 NIH/NCRR UL1 TR000124 – UCLA Clinical and Translational Science Institute (CTSI) Voucher “A mouse toxicity study of a novel drug candidate”
  • 2015-2016 Cure Alzheimer’s Fund 20152631 “Optimization of pharmacologic properties of molecular tweezers”
  • 2015-2017 CurePSP Foundation 600-6-15 “Small-molecule modulation of tau clearance and aggregation”
  • 2015-2020 NIH/NIA R01AG050721 “Misfolded protein clearance enhancers for Alzheimer’s therapy”

Bitan, Gal, Ph.D.
University California, Los Angeles, Alzheimer's Disease Research Center - Design and Development of Structure-Based Small Molecule Inhibitors of Amyloid Assembly, Gal Bitan, PhD Professor in Residence of Neurology, David Geffen School of Medicine at UCLA
Member of Brain Research Institute at UCLA
Member of Interdepartmental Ph.D. Program in Neuroscience at UCLA
Associate Member of Molecular Biology Institute at UCLA
Specialty: Chemistry and Biochemistry.
Tel: (310) 206-2082
Fax: (310) 206-1700
Email:
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