Gal Bitan, Ph.D.

Titles

Associate Professor, Neurology
Neuroscience IDP
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 SouthLos Angeles, CA 90095UNITED STATES

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 bone-related 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 amyloid-related diseases, including 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. For example, Aß oligomers have been found in brains of Alzheimer's disease patients but not in those of age-matched healthy individuals. 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 2003, Dr. Bitan was appointed as an Instructor in Neurology in the Center for Neurologic Disease at Brigham and Women's Hospital and Harvard Medical School. In 2004, Dr. Bitan joined UCLA where he is currently an Associate Professor of Neurology in the David Geffen School of Medicine. In recognition of his achievements, in 2005, Dr. Bitan received the Turken research award for the study of Alzheimer's disease.

Publications:

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; E-pub ahead of print, DOI: 10.2174/13816128113199990496.
A Attar, W-TC Chan, F-G Klrner, 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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N Ferreira, A Pereira-Henriques, A Attar, F-G Klrner, 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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S Acharya, BM Safaie, P Wongkongkathep, MI Ivanova, A Attar, F-G Klrner, 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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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 Alzheimers 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 Klrner, 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.
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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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.
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 Klrner, 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 Alzheimers 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 Klrner, T Schrader, SA Frautschy, C Grassi and G Bitan   Protection of primary neurons and mouse brain from Alzheimers 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 assembliescommon 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): 1068710697.
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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 Klrner, 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): 1695816969.
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K Hochdrffer, J Mrz-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 Aβ142 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 Aggregationanalytical 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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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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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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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.
Bitan G, Scheibler L, Mierke DF, Rosenblatt M, and Chorev M   Ligand--Integrin αVβ3 Interaction Determined by Photoaffinity Crosslinking: A Challenge to the Prevailing Model Biochemistry, 2000; 39: 11014-11023.
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Bitan G, Scheibler L, Greenberg Z, Teng H, Rosenblatt M, and Chorev M   Mapping the Integrin αVβ3--Ligand Interface by Photoaffinity Cross-linking Biochemistry, 1999; 38: 3414-3420.
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Bitan G, Zeltser I, Byk G, Halle D, Mashriki Y, Gluhov EV, Sukhotinsky I, Hanani M, Selinger Z, and Gilon C   Backbone cyclization of the C-terminal part of substance P. Part 1: The important role of the sulphur in position 11 J. Pept. Sci, 1996; 2(4): 261-269.
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Bitan G, Behrens S, Matha B, Mashriki Y, Hanani H, Kessler H, and Gilon C   New Backbone-Cyclic Substance P Analogs Lett. Pept. Sci, 1995; 2: 121-124.
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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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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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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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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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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, 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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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, Sukhotinsky I, Mashriki Y, Hanani M, Selinger Z, and Gilon C   Synthesis and biological activity of novel backbone-bicyclic substance-P analogs containing lactam and disulfide bridges J. Pept. Res, 1997; 49(5): 421-426.
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Byk G, Halle D, Zeltser I, Bitan G, Selinger Z, and Gilon C   Synthesis and biological activity of NK-1 selective, N-backbone cyclic analogs of the C-terminal hexapeptide of substance P J. Med. Chem, 1996; 39(16): 3174-3178.
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