COMPLETED: Studying the Physical Chemistry of Amyloid-β Aggregation

Purpose

The laboratories of Easton Center investigators David Teplow, Ph.D. and Gal Bitan Ph.D. focus on characterizing the subcellular interactions of the amyloid beta (Aß) protein --- considered by most to be the proximate cause of Alzheimer's disease (AD). This in vitro and in silico research examines the physical chemistry that leads to the tendency for Aß aggregate and become neurotoxic. Dr. Bitan is specifically investigating mechanisms for intervening in the aggregation process to reduce toxicity using a "tweezer" compound, which acts to interfere with a loop structure in the amyloid molecule necessary for protein aggregation and neurotoxicity.

For more information, please contact This email address is being protected from spambots. You need JavaScript enabled to view it. or This email address is being protected from spambots. You need JavaScript enabled to view it. at (310) 206-2082.

Publications:

  • MM Condron, BH Monien, and G Bitan (2008) Synthesis and purification of highly hydrophobic peptides derived from the C-terminus of amyloid β-protein, Open Biotechnol, J., 2:87-93.
  • A Shanmugam, BH Monien, and G Bitan (2008) Development in Diagnostic and Therapeutic Strategies for Alzheimer’s Disease. In: Sun M-K, Ed. Research Progress in Alzheimer’s Disease and Dementia. Vol. 3. Nova Science Publisher, Inc. pp. 193-250.
  • EA Fradinger, BH Monien, B Urbanc, A Lomakin, M Tan, H Li, SM Spring, MM Condron, L Cruz, C- W Xie, GB Benedek, and G Bitan (2008) C-terminal peptides co-assemble into Aβ42 oligomers and protect neurons against Aβ42-induced neurotoxicity, Proc. Natl. Acad. Sci. USA, 105:14175–14180.
  • F Rahimi, A Shuanmugam, and G Bitan (2008) Structure–Function Relationships of Pre-Fibrillar Protein Assemblies in Alzheimer's Disease and Related Disorders. Curr. Alz. Res. 5: 319-341.
  • C Wu, SL Bernstein, M Murray, MM Condron, G Bitan, MT Bowers, and J-E Shea (2009) Structural characterization of Amyloid β-protein C-terminal fragments, J. Mol. Biol., 387:492-501.
  • H Li, F Rahimi, K Murakami, P Maiti, S Sinha, and G Bitan (2009) Amyloids and protein aggregation –analytical methods. In Encyclopedia of Analytical Chemistry, S1-S3, RA Meyers, Ed. Chichester, UK, John Wiley & Sons Ltd., pp. 635-666.
  • SL Bernstein, NF Dupuis, ND Lazo, T Wyttenbach, MM Condron, G Bitan, DB Teplow, J-E Shea, BT. Ruotolo, CV. Robinson, and MT Bowers (2009) Amyloid-β protein oligomerization and the importance of tetramers and dodecamers in the aetiology of Alzheimer’s disease, Nat. Chem. 1: 326- 331.
  • H Li, BH Monien, EA Fradinger, B Urbanc and G Bitan (2010) Biophysical Characterization of Aβ42 C-terminal Fragments—Inhibitors of Aβ42 Neurotoxicity, Biochemistry, 49: 1259-1267.
  • B. Urbanc, M Bentel, L. Cruz, G Bitan, and DB Teplow (2010) Elucidation of amyloid β-protein oligomerization mechanisms: Discrete Molecular Dynamics Study, J. Am. Chem. Soc. 1312: 4266- 4280.
  • H Li, BH Monien, A Lomakin, R Zemel, EA Fradinger, M Tan, SM Spring, B Urbanc, C-W Xie, GB Benedek, and G Bitan (2010) Mechanistic Investigation of the Inhibition of Aβ42 Assembly and Neurotoxicity by Aβ42 C-terminal Fragments. Biochemistry, 49: 6358-6364.
  • B Urbanc, M Bentel, L Cruz, H Li, EA Fradinger BH Monien, and G Bitan (2011) In silico study of Aβ1−42 oligomer formation in the presence of Aβ-derived toxicity inhibitors. J. Mol. Biol., 410: 316– 328.
  • H Li, Z Du, DHJ Lopes, EA Fradinger, C Wang, and G Bitan. C-terminal Tetrapeptides Inhibit Aβ42- induced Neurotoxicity Primarily Through Specific Interaction at the N-terminus of Aβ42. (2011) J. Med. Chem., 54: 8451-8460.
  • MM Gessel, C Wu, H Li, G Bitan, J-E Shea, and MT Bowers (2012) Aβ(39-42) Modulates Aβ Oligomerization but not Fibril Formation. Biochemistry, 51: 108-117.
  • F Rahimi and G Bitan (2012) The structure and function of fibrillar and oligomeric assemblies of amyloidogenic proteins. In: Pre-fibrillar amyloidogenic protein assemblies—common cytotoxins underlying degenerative diseases. F Rahimi and G Bitan, Eds. Springer Science+Media B.V., Dordrecht. pp. 1-36.
  • C Rosensweig, K Ono, K Murakami, DK Lowenstein, G Bitan, and DB Teplow. Preparation of stable amyloid β-protein oligomers of defined assembly order (2012) Methods Mol. Biol. 489: 23-31.
  • H Li, R Zemel, DHJ Lopes, BH Monien, and G Bitan (2012) A two-step strategy for SAR studies of N-methylated Aβ42 C-terminal fragments as Aβ42 toxicity inhibitors. ChemMedChem, 7: 515-522.
  • I Solomonov, E Korkotian, B Born, D Kaganovich, Y Feldman, A Bitler, AF Rahimi, H Li, G Bitan, and I Sagi (2012) Zn2+-Aβ complexes form metastable quasi-spherical oligomers that are cytotoxic to cultured hippocampal neurons, J. Biol. Chem., 287: 20555-20564.
  • F Rahimi and G Bitan (2014) Methods for studying and structure–function relationships of non- fibrillar protein assemblies in Alzheimer's disease and related disorders. In: Advances in Alzheimer Research. Vol. 2, DK Lahiri Ed. Bentham Scientific. Pp. 291-374.
  • R Malishev, S Nandi, S Kolusheva, Y Levi-Kalisman, F-G Klärner, T Schrader, G Bitan*, and R Jelinek* (2015) Toxicity inhibitors protect lipid membranes from disruption by Aβ42, ACS Chem. Neurosci. 6: 1860-1869.
  • X Zheng, C Wu, D Liu, H Li, G Bitan, J-E Shea and MT Bowers (2015) Mechanism of C-Terminal Fragments of Amyloid β-Protein as Aβ Inhibitors: C-Terminal Interactions Play a Key Role in Their Inhibitory Activity, J. Phys. Chem. B, 120: 1615-1623.
  • F Rahimi, H Li, S Sinha, and G Bitan (2016) Modulators of amyloid β-protein (Aβ) self-assembly. In: Developing Therapeutics for Alzheimer’s Disease, 1st Edition. MS Wolfe Ed., Elsevier/Academic Press. Pp. 97–191.
  • H Li, F Rahimi, and G Bitan (2016) Modulation of amyloid β-protein (Aβ) assembly by homologous C-terminal fragments as a strategy for inhibiting Aβ toxicity. ACS Chem. Neurosci. 7: 845–856.
  • EY Hayden, JL Conovaloff, A Mason, G Bitan, and DB Teplow (2017) Preparation of pure populations of covalently stabilized amyloid β-protein oligomers of specific sizes. Anal. Biochem., 518: 78-85.
  • EY Hayden, JL Conovaloff, A Mason, G Bitan, and DB Teplow (2018) Preparation of pure populations of amyloid b-protein oligomers of defined size. Methods Mol. Biol., 1779: 3-12.
  • 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.

Health Professionals