Site Search



Gal Bitan, Ph.D.

Work Email Address:
gbitan@mednet.ucla.edu

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

Work Phone Number:
310-206 2082



Login to the Faculty Database

Department / Division Affiliations
Associate Professor, Neurology, Neuroscience IDP
Member, Access Biochemistry, Biophysics, Structural Biology Home Area, ACCESS Program, Access Molecular Pharmacology: Therapeutics, Diagnostics, and Biology of Disease Home Area, Access Neuroscience Home Area, Brain Research Institute, Pharmacology Home Area

The Bitan Laboratory focuses on structure-based design of new therapeutic agents for neurodegenerative diseases, including Alzheimer's, Parkinson's, ALS, and others. Our laboratory examines novel molecules and explores their potential for diagnostic and therapeutic uses. These efforts are guided by structural knowledge obtained though multifaceted experimental and theoretical studies involving collaborations with many groups around the world. Dr. Bitan's laboratory is currently developing an experimental drug that may prevent and effectively treat Alzheimer's, Parkinson's, and other degenerative diseases.

Bio:

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, 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.
Download
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.
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; E-pub ahead of print. DOI 10.1007/s13311-013-0256-8.
Download
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.
Download
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.
Download
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.
Download
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.
Download
A Attar, F Rahimi, and G Bitan Modulators of amyloid protein aggregation and toxicity: EGCG and CLR01. Translational Neuroscience. 2013; 4(4): 385-409.
Download
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.
Download
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.
Download
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.
H Li, R Zemel, DHJ Lopes, BH Monien, and G Bitan A Two-Step Strategy for Structure–Activity Relationship Studies of N-Methylated Aβ42 C-Terminal Fragments as Aβ42 Toxicity Inhibitors. ChemMedChem. 2012; 7: 515-522.
Download
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.
Download
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.
Download
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.
Download
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.
Download
T Liu and G Bitan Modulating Self-Assembly of Amyloidogenic Proteins as a Therapeutic Approach for Neurodegenerative Diseases: Strategies and Mechanisms. ChemMedChem. 2012; 7: 359-374.
Download
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.
Download
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.
Download
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.
Download
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.
Download
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.
Download
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.
Download
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.
Download
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.
Download
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.
Download
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.
Download
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.
Download
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.
Download
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.
Download
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.
Download
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.
Download
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.
Download
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.
Download
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.
Download
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.
Download
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.
Download
Rahimi F, Shanmugam A, and Bitan G Structure-Function Relationships of Pre-Fibrillar Protein Assemblies in Alzheimer's Disease and Related Disorders. Curr. Alz. Res. 2008; 5(3): 319-341.
Download
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.
Download
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.
Download
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.
Download
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.
Download
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.
Download
Bitan G Structural study of metastable amyloidogenic protein oligomers by Photo-Induced Cross-linking of Unmodified Proteins. Methods Enzymol. 2006; 413: 217-236.
Download
Vollers SS, Teplow DB, and Bitan G Determination of peptide oligomerization state using rapid photochemical cross-linking. Methods Mol. Biol. 2005; 299: 11-18.
Download
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.
Download
Bitan G and Teplow DB Preparation of aggregate-free, low molecular weight amyloid-β for assembly and toxicity assays. Methods Mol. Biol. 2005; 299: 3-9.
Download
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.
Download
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.
Download
Muller D, Zeltser I, Bitan G, and Gilon C Building Units for N-Backbone Cyclic Peptides. Part 3. Synthesis of Protected Nα-ω-carboxyalkylene and Nα-ω-aminoalkylene Amino Acids. J. Org. Chem. 1997; 62: 411-416.
Download
Bitan G, Muller D, Kasher R, Gluhov EV, and Gilon C Building Units for N-Backbone Cyclic Peptides. Part 4. Synthesis of Protected Nα-ω-functionalized alkylamino acids by reductive alkylation of natural amino acids. J. Chem. Soc. Perkin Trans. 1. 1997; 1501-1510.
Download
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.
Download
Bitan G and Gilon C Building Units for N-Backbone Cyclic Peptides. Part 2. Synthesis of Protected Nα-ω-thioalkylene Amino Acids and Their Incorporation into Dipeptide Units. Tetrahedron. 1995; 51: 10513-10522.
Download
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.
Download
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.
Download
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.
Download
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.
Download
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.
Download
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.
Download
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.
Download
Bitan G and Teplow DB Rapid photochemical cross-linking--a new tool for studies of metastable, amyloidogenic protein assemblies. Acc. Chem. Res. 2004; 37(6): 357-364.
Download
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.
Download
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.
Download
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.
Download
Kirkitadze MD, Bitan G, and Teplow DB Paradigm shifts in Alzheimer's disease and other neurodegenerative disorders: the emerging role of oligomeric assemblies. J. Neurosci. Res. 2002; 69(5): 567-577.
Download
Bitan G, Lomakin A, and Teplow DB Amyloid β-protein oligomerization: prenucleation interactions revealed by photo-induced cross-linking of unmodified proteins. J. Biol. Chem. 2001; 276(37): 35176-35184.
Download
Bitan G, Scheibler L, Teng H, Rosenblatt M, and Chorev M Design and evaluation of benzophenone-containing conformationally constrained ligands as tools for photoaffinity scanning of the integrin αVβ3-ligand bimolecular interaction. J. Pept. Res. 2000; 55(3): 181-194.
Download
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.
Download
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.
Download