Gal Bitan, Ph.D.

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Titles

Professor In-Residence, Neurology

Member, Biochemistry, Biophysics & Structural Biology GPB Home Area

Brain Research Institute

Molecular Pharmacology GPB Home Area

Neuroscience GPB Home Area

Contact Information

Email
gbitan@mednet.ucla.edu
Phone
Work Phone Number: 310-206 2082
Address

Mailing Address:

635 Charles E Young Drive South
Los Angeles, CA 90095
UNITED STATES

Website
http://bitanlab.neurology.ucla.edu

Biography

Gal Bitan completed his graduate studies in organic chemistry at the Hebrew University of Jerusalem, Israel. Dr. Bitan's graduate work on unnatural amino acids and non-conventional peptide cyclization methodologies led him to postdoctoral studies on the structural biology of ligand-receptor systems including integrins and G protein-coupled receptors at Clark University, Worcester, MA and Beth Israel-Deaconess Medical Center/Harvard Medical School, Boston, MA. Dr. Bitan then moved on to tackle the problem of protein misfolding and aggregation, which is involved in over 30 devastating diseases, such as Alzheimer's disease, Parkinson's disease, prion diseases (e.g., Mad Cow disease), amyotrophic lateral sclerosis (Lou Gherig's disease), and type II diabetes. Working at Brigham and Women's Hospital/Harvard Medical School, Boston, MA, Dr. Bitan has made fundamental contributions to the study of early events in the pathologic cascades that cause Alzheimer's disease. In Alzheimer's disease, the amyloid ß-protein (Aß) self-associates to form a variety of oligomeric and polymeric structures with potent neurotoxic activities. In particular, Aß oligomers have been implicated as the probable cause of Alzheimer's disease. Dr. Bitan introduced the use of novel photochemical protein cross-linking techniques for investigation of Aß assembly and discovered one of the earliest oligomers in the assembly cascade, the paranucleus. In 2004, Dr. Bitan joined UCLA where he is currently an Associate Professor of Neurology. His research program is focused on translational science geared at developing novel, mechanism-based diagnostic and therapeutic tools for neurodegenerative diseases, including Alzheimer's disease and other tauopathies, Parkinson's disease, multiple system atrophy, and amyotrophic lateral sclerosis.

Publications

AE Röcker, JA.Müller, E Dietzel, M Harms, F Krüger, C Heid, A Sowisolk, C Frich-Riber, A Kupke3, S Lippold4, J von Einem, J Beer, B Knöll, S Becker, J Schmidt-Chanasit, M Otto, O Vapalahti, AN Zelikin, G Bitan, T Schrader and J Münch   The molecular tweezer CLR01 inhibits Ebola and Zika virus infection Antiviral Res, 2018; in press.
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RR Walsh, F Krismer, WR Galpern, GK Wenning, PA Low, G Halliday, WJ Koroshetz, J Holton, NP Quinn, O Rascol, LM Shaw, D Eidelberg, P Bower, JL Cummings, V Abler, J Biedenharn, G Bitan, DJ Brooks, P Brundin, H Fernandez, P Fortier, R Freeman, T Gasser, A Hewitt, GU Höglinger, MJ Huentelman, PH Jensen, A Jeromin, UJ Kang, H Kaufmann, L Kellerman, V Khurana, T Klockgether, WScott Kim, C Langer, P LeWitt, E Masliah, W Meissner, R Melki, S Ostrowitzki, S Piantadosi, W Poewe, D Robertson, C Roemer, D Schenk, M Schlossmacher, JD Schmahmann, K Seppi, L Shih, A Siderowf, GT Stebbins, N Stefanova, S Tsuji, S Sutton and J Zhang   Recommendations of the Global Multiple System Atrophy Research Roadmap Meeting Neurology, 2018; in press.
F Richter, I Magen, P Lee, S Subramaniam, J Hayes, A Attar, C Zhu, N Franich, N Bove, K De La Rosa, J Kwong, F-G Klärner, T Schrader, M- F Chesselet, and G Bitan   A molecular tweezer ameliorates motor deficits in mice overexpressing α-synuclein Neurotherapeutics, 2017; 14: 1107-1119.
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MU Daloglu, A Ray, Z Gorocs, M Xiong, R Malik, G Bitan, E McLeod, and A Ozcan   Computational On-Chip Imaging of Nanoparticles and Bio-molecules using Ultraviolet Light Sci. Reports, 2017; 7: 44157.
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T Vöpel, K Bravo-Rodriguez, S Mittal, S Vachharajani, D Gnutt, A Sharma, A Steinhoff, F Oluwaseun, G Ellrichmann, N Nshinian, C Heid, JA Loo, F-G Klärner, T Schrader, G Bitan, EE Wanker, S Ebbinghaus, and E Sanchez-Garcia   Inhibition of Huntingtin aggregation by the molecular tweezer CLR01 J. Am. Chem. Soc, 2017; 139: 5640–5643.
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N Xu, G Bitan, T Schrader, F-G Klärner, H Osinska, and J Robbins   Inhibition of Mutant αB Crystallin-Induced Protein Aggregation by a Molecular Tweezer J. Am. Heart Assoc, 2017; 6: e006182.
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EY Hayden, JL Conovaloff, A Mason, G Bitan, DB Teplow   Preparation of pure populations of covalently stabilized amyloid β-protein oligomers of specific sizes Anal. Biochem, 2017; 518: 78-85.
F. Rahimi, H. Li, S. Sinha, and G. Bitan   Modulators of Amyloid β-Protein (Aβ) Self-Assembly in: Developing Therapeutics for Alzheimer's Disease: Progress and Challenges, 2016; 97-191.
T Schrader, G Bitan, and F-G Klärner   Molecular Tweezers for Lysine and Arginine – Powerful Inhibitors of Pathologic Protein Aggregation Chem. Commun, 2016; 52(76): 11318-11334.
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A Lulla, L Barnhill, G Bitan, MI Ivanova, B Nguyen, K O’Donnell, MC. Stahl, C Yamashiro, F-G Klärner, T Schrader, A Sagasti, and JM Bronstein   Neurotoxicity of the Parkinson’s Disease-Associated Pesticide Ziram Is Synuclein-Dependent in Zebrafish Embryos Environ. Health Perspect, 2016; 124: 1766-1775.
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SM Fogerson, AJ van Brummen, DJ Busch, SR Allen, R Roychaudhuri, S Banks, F-G Klärner, T Schrader, G Bitan, and JR Morgan   Reducing synuclein accumulation after spinal cord injury improves neuronal survival and axon regeneration Exp. Neurol, 2016; 278: 105-115.
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E Lump, LM Castellano, C Meier, J Seeliger, N Erwin, B Sperlich, CM Stürzel, S Usmani, RM Hammond, J von Einem, G Gerold, F Kreppel, K Bravo-Rodriguez, T Pietschmann, VM Holmes, D Palesch, O Zirafi, D Weissman, A Sowislok, B Wettig, C Heid, F Kirchhoff, T Weil, F-G Klärner, T Schrader, G Bitan, E Sanchez-Garcia, R Winter, J Shorter, and Jan Münch   A molecular tweezer antagonizes seminal amyloids and HIV infection eLife, 2015; (4): e05397.
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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. B, 2015; 119(14): 4831-4841.
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X Zheng, C Wu, D Liu, H Li, G Bitan, J-E Shea, and MT Bowers   Mechanism of C-Terminal Fragments of Amyloid β-Protein as Aβ Inhibitors: Do C-Terminal Interactions Play a Key Role in Their Inhibitory Activity? J. Phys. Chem. B, 2015; 120(8): 1615-1623.
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DHJ Lopes, A Attar, G Nair, EY Hayden, Z Du, K McDaniel, S Dutt, H Bandmann, K Bravo-Rodriguez, S Mittal, F-G Klärner, C Wang, E Sánchez-García, T Schrader, and G Bitan   Molecular tweezers inhibit islet amyloid polypeptide assembly and toxicity by a new mechanism ACS Chem. Biol, 2015; 10(6): 1555-1569.
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R Roychaudhuri, X Zheng, A Lomakin, P Maiti, MM Condron, GB Benedek, G Bitan, MT Bowers, and DB Teplow   Role of species-specific primary structure differences in Aβ42 assembly and neurotoxicity ACS Chem. Neurosci, 2015; 6: 1941-1955.
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G Herzog, MD Shmueli, L Levy, L Engel, E Gazit, F-G Klärner, T Schrader, G Bitan, and D Segal   The Lys-specific molecular tweezer, CLR01, modulates aggregation of mutant p53 DNA binding domain and inhibits its toxicity Biochemistry, 2015; 54(24): 3729–3738.
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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.
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S Acharya, BM Safaie, P Wongkongkathep, MI Ivanova, A Attar, F-G Klärner, T Schrader, JA Loo, G Bitan, and LJ Lapidus   Molecular Basis for Preventing α-Synuclein Aggregation by a Molecular Tweezer J. Biol. Chem, 2014; 289(15): 10727-10737.
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N Ferreira, A Pereira-Henriques, A Attar, F-G Klärner, T Schrader, G Bitan, L Gales, MJ Saraiva, and MR Almeida   Molecular Tweezers Targeting Transthyretin Amyloidosis Neurotherapeutics, 2014; 11: 450-461.
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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. Tox, 2014; 15(23): doi:10.1186/2050-6511-15-23.
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A Attar, T Liu, W-T C Chan, J Hayes, M Nejad, K Lei, and G Bitan   A Shortened Barnes Maze Protocol Reveals Memory Deficits at 4-Months of Age in the Triple-Transgenic Mouse Model of Alzheimer's Disease PLoS ONE, 2013; 8(11): e80355.
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A Attar, D Meral, B Urbanc, and G Bitan   Assembly of Amyloid β-Protein Variants Containing Familial Alzheimer’s Disease-Linked Amino Acid Substitutions In: Bio-nanoimaging - Protein Misfolding & Aggregation, 2013; 429-442.
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C Ripoli, R Piacentini, E Riccardi, L Leone, DDL Puma, G Bitan, and C Grassi   Effects of different amyloid β-protein analogues on synaptic function Neurobiol. Aging, 2013; 34: 1032-1044.
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A Attar, F Rahimi, and G Bitan   Modulators of amyloid protein aggregation and toxicity: EGCG and CLR01 Translational Neuroscience, 2013; 4(4): 385-409.
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CR Connors, DJ Rosenman, DHJ Lopes, S Mittal, G Bitan, M Sorci, G Belfort, A Garcia, and C Wang   Tranilast Binds to Aβ Monomers and Promotes Aβ Fibrillation Biochemistry, 2013; 52: 3995-4002.
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S Sinha, DHJ Lopes, and G Bitan   A Key Role for Lysine Residues in Amyloid β-Protein Folding, Assembly, and Toxicity ACS Chem. Neurosci, 2012; 3(6): 473-481.
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S Prabhudesai*, S Sinha*, A Attar, A Kotagiri, AG Fitzmaurice, R Lakshmanan, MI Ivanova, JA Loo, F-G Klärner, T Schrader, M Stahl, G Bitan#, and JM Bronstein#   A Novel “Molecular Tweezer” Inhibitor of α-Synuclein Neurotoxicity in Vitro and in Vivo Neurotherapeutics, 2012; 9(2): 464-476.
DHJ Lopes, S Sinha, C Rosensweig, and G Bitan   Application of Photochemical Cross-linking to the Study of Oligomerization of Amyloidogenic Proteins Methods Mol. Biol, 2012; 489: 11-22.
MM Gessel*, C Wu*, H Li*, G Bitan, J-E Shea, and MT Bowers   Aβ(39−42) Modulates Aβ Oligomerization but Not Fibril Formation Biochemistry, 2012; 51(1): 108-118.
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G Bitan   Can We Accelerate the Path towards Therapy for Amyloid-Related Disease? J. Gerontol. Geriatr. Res, 2012; 1(2): doi: 10.4172/jggr.1000e106.
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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. Neurosci, 2012; 3(6): 451-458.
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PA Novick*, DH Lopes*, KM Branson, A Estera-Chopo, IA Graef, G Bitan, and VS Pande   Design of β-Amyloid Aggregation Inhibitors from a Predicted Structural Motif J. Med. Chem, 2012; 55: 3002-3010.
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JM Ringman, AT Fithian, K Gylys, JL Cummings, G Coppola, D Elashoff, D Pratico, J Moskovitz, and G Bitan   Plasma Methionine Sulfoxide in Persons with Familial Alzheimer’s Disease Mutations Dement. Geriatr. Cogn. Disord, 2012; 33(4): 219-225.
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C Rosensweig, K Ono, K Murakami, D Lowenstein, G Bitan, and DB Teplow   Preparation of stable amyloid β-protein oligomers of defined assembly order Methods Mol. Biol, 2012; 489: 23-31.
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 Brain, 2012; 135(Pt 12): 3735-3748.
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F Rahimi and G Bitan   The structure and function of fibrillar and oligomeric assemblies of amyloidogenic proteins In: Pre-fibrillar amyloidogenic protein assemblies—common cytotoxins underlying degenerative diseases, 2012; 1-36.
I Solomonov, E Korkotian, B Born, Y Feldman, A Bitler, F Rahimi, H Li, G Bitan, and I Sagi   Zn2+-Aβ40 complexes form metastable quasi-spherical oligomers that are cytotoxic to cultured hippocampal neurons J. Biol. Chem, 2012; 287(24): 20555-20564.
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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 J. Med. Chem, 2011; 54: 8451-8460.
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J Moskovitz, P Maiti, DHJ Lopes, DB Oien, A Attar, T Liu, S Mittal, J Hayes, and G Bitan   Induction of Methionine-Sulfoxide Reductases Protects Neurons from Amyloid β-Protein Insults in Vitro and in Vivo Biochemistry, 2011; 50(49): 10687–10697.
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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. Soc, 2011; 133(42): 16958–16969.
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K Hochdörffer, J März-Berberic, L Nagel-Steger, M Epple, W Meyer-Zaika, AHC Horn, H Sticht, S Sinha, G Bitan, and T Schrader   Rational Design of β-Sheet Ligands Against Aβ42-Induced Toxicity J. Am. Chem. Soc, 2011; 133: 4348-4358.
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B Urbanc, M Betnel, L Cruz, H Li, EA Fradinger, BH Monien, and G Bitan   Structural Basis for Aβ1–42 Toxicity Inhibition by Aβ C-Terminal Fragments: Discrete Molecular Dynamics Study J. Mol. Biol, 2011; 410(2): 316-328.
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Li H, Monien BH, Fradinger EA, Urbanc B, and Bitan G   Biophysical Characterization of Aβ42 C-Terminal Fragments: Inhibitors of Aβ42 Neurotoxicity Biochemistry, 2010; 49: 159-1267.
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Maiti P, Lomakin A, Benedek GB, and Bitan G   Despite its role in assembly, methionine 35 is not necessary for amyloid β-protein toxicity J. Neurochem, 2010; 113: 1252-1262.
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Urbanc B, Bentel M, Cruz L, Bitan G, and Teplow DB   Elucidation of Amyloid β-Protein Oligomerization Mechanisms: Discrete Molecular Dynamics Study J. Am. Chem. Soc, 2010; 132: 4266-4280.
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Li H, Monien BH, Lomakin A, Zemel R, Fradinger EA, Tan M, Spring SM, Urbanc B, Xie C-W, Benedek GB, and Bitan G   Mechanistic Investigation of the Inhibition of Aβ42 Assembly and Neurotoxicity by Aβ42 C-Terminal Fragments Biochemistry, 2010; 49(30): 6358-6364.
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Rahimi F and Bitan G   Selection of Aptamers for Amyloid β-Protein, the Causative Agent of Alzheimer's Disease J. Vis. Exp, 2010; (39): doi: 10.3791/1955.
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P Maiti, R Piacentini, C Ripoli, C Grassi, and G Bitan   Surprising toxicity and assembly behavior of amyloid β-protein oxidized to sulfone Biochem. J, 2010; 443(2): 323-332.
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Maji SK, Orgozalek Loo RR, Inayatullah M, Spring SM, Vollers SS, Condron MM, Bitan G, Loo JA, and Teplow DB.   Amino acid position-specific contributions to amyloid β-protein oligomerization J. Biol. Chem, 2009; 284: 23580-23591.
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Bernstein SL, Dupuis NF, Lazo ND, Wyttenbach T, Condron MM, Bitan G , Teplow DB, Shea J-E, Ruotolo BT, Robinson CV, and Bowers MT.   Amyloid β-protein oligomerization and the importance of tetramers and dodecamers in the aetiology of Alzheimer's disease Nat. Chem, 2009; 1(4): 326-331.
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Li H, Rahimi F, Sinha S, Maiti P, Murakami K, and Bitan G.   Amyloids and Protein Aggregation—analytical methods Encyclopedia Anal. Chem, 2009; Published online, DOI: 10.1002/9780470027318.a9038.
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Rahimi F, Maiti P, and Bitan G.   Photo-Induced Cross-Linking of Unmodified Proteins (PICUP) Applied to Amyloidogenic Peptides J. Vis. Exp, 2009; (23): doi: 10.3791/1071.
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Rahimi F, Murakami K, Summers JL, Chen C-HB, and Bitan G.   RNA Aptamers Generated against Oligomeric Aβ40 Recognize Common Amyloid Aptatopes with Low Specificity but High Sensitivity PLoS ONE, 2009; 4(11): doi:10.1371/journal.pone.0007694.
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Wu* C, Murray* MM, Bernstein* SL, Condron MM, Bitan G, Bowers MT, and Shea J-E.   The Structure of Aβ42 C-Terminal Fragments Probed by a Combined Experimental and Theoretical Study J. Mol. Biol, 2009; 387(2): 492-501.
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Fradinger EA*, Monien BH*, Urbanc B, Lomakin A, Tan M, Li H, Spring SM, Condron MM, Cruz L, Xie, C-W, Benedek GB, and Bitan G   C-terminal peptides co-assemble into Aβ42 oligomers and protect neurons against Aβ42-induced neurotoxicity Proc. Natl. Acad. Sci. USA, 2008; 105(37): 14175-14180.
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Shanmugam A, Monien BH, and Bitan G   Development in Diagnostic and Therapeutic Strategies for Alzheimer's Disease in Research Progress in Alzheimer's Disease and Dementia, 2008; 3: 193-250.
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Condron MM, Monien BH, and Bitan G   Synthesis and Purification of Highly Hydrophobic Peptides Derived from the C-Terminus of Amyloid β-Protein Open Biotechnol. J, 2008; 2(1): 87-93.
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Seabrook TJ, Thomas K, Jiang L, Bloom J, Spooner E, Maier M, Bitan G, and Lemere CA   Dendrimeric Aβ1-15 is an effective immunogen in wildtype and APP-tg mice Neurobiol. Aging, 2007; 28(6): 813-823.
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Yun S, Urbanc B, Cruz L, Bitan G, Teplow DB, and Stanely HS   Role of Electrostatic Interactions in Amyloid β-Protein (Aβ) Oligomer Formation: A Discrete Molecular Dynamics Study Biophys. J, 2007; 94: 4064-4077.
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Baumketner A, Bernstein SL, Wyttenbach T, Bitan G, Teplow DB, Bowers MT, and Shea J-E   Amyloid β-protein monomer structure: A computational and experimental study Prot. Sci, 2006; 15: 420-428.
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Monien BH, Apostolova LG, and Bitan G   Early diagnostics and therapeutics for Alzheimer's disease - how early can we get there? Expert Rev. Neurother, 2006; 6(9): 1293-1306.
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Teplow DB, Lazo ND, Bitan G, Bernstein S, Wyttenbach T, Bowers MT, Baumketner A, Shea J-E, Urbanc B, Cruz L, Borreguero J, and Stanley HE   Elucidating Amyloid β-Protein Folding and Assembly: A Multidisciplinary Approach Acc. Chem. Res, 2006; 39(9): 635-345.
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Bernstein SL, Wyttenbach T, Baumketner A, Shea J-E, Bitan G, Teplow DB, and Bowers MT   Amyloid β-protein: monomer structure and early aggregation states of Aβ42 and its Pro19 alloform J. Am. Chem. Soc, 2005; 127(7): 2075-2084.
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Vollers SS, Teplow DB, and Bitan G   Determination of peptide oligomerization state using rapid photochemical cross-linking Methods Mol. Biol, 2005; 299: 11-18.
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Fradinger EA and Bitan G   En route to early diagnosis of Alzheimer's disease--are we there yet? Trends Biotech, 2005; 23(11): 531-533.
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Bitan G, Fradinger EA, Spring SM, and Teplow DB   Neurotoxic protein oligomers-what you see is not always what you get Amyloid, 2005; 12: 88-95.
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Lazo ND, Maji SK, Fradinger EA, Bitan G, and Teplow DB   The Amyloid β-protein In: Sipe J, Ed. Amyloid Proteins: the β-sheet Conformation and Disease, 2005; 385-492.
Urbanc B, Cruz L, Yun S, Buldyrev SV, Bitan G, Teplow DB, and Stanley HE   In silico study of amyloid β-protein folding and oligomerization Proc. Natl. Acad. Sci. USA, 2004; 101(50): 17345-17350.
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Bitan G, Tarus B, Vollers SS, Lashuel HA, Condron MM, Straub JE, and Teplow DB   A molecular switch in amyloid assembly: Met35 and amyloid β-protein oligomerization J. Am. Chem. Soc, 2003; 125(50): 15359-15365.
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Bitan G, Kirkitadze MD, Lomakin A, Vollers SS, Benedek GB, and Teplow DB   Amyloid β-protein (Aβ) assembly: Aβ40 and Aβ42 oligomerize through distinct pathways Proc. Natl. Acad. Sci. USA, 2003; 100(1): 330-335.
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Bitan G, Vollers SS, and Teplow DB   Elucidation of primary structure elements controlling early amyloid β-protein oligomerization J. Biol. Chem, 2003; 278(37): 34882-34889.
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