Professor of Clinical Biochemistry, Sackler Faculty of Medicine
Lily and Avraham Gildor Chair for the Investigation of Growth Factors
Director, Levie-Edershein-Gitter Institute for Functional Brain Imaging
Director, Dr. Diana and Zelman Elton Laboratory for Molecular Neuroendocrinology
Editor-in-Chief, Journal of Molecular Neuroscience
Neuronal Plasticity and Nerve Cell Protection in Disease
Our research is characterized by a multi-level approach to the study of brain function, behavior, memory and drug discovery, from molecules to cures. Targeting autism, schizophrenia as well as Alzheimer’s disease and related neurodegeneration and utilizing a multidisciplinary approach, our group investigates different aspects of neuronal plasticity and nerve cell protection, at the molecular, cellular and system level.
A major focus in the laboratory is on nerve structure and transport mechanisms. We have discovered novel families of proteins associated with cross talk among nerve cells and their support cells, including activity-dependent neurotrophic factor (ADNF) and activity-dependent neuroprotetive proteins (ADNPs, with ADNP being a major gene mutated in autism). Small ADNF and ADNP derivatives are in clinical development. The lead compound, davunetide is planned for an advanced Phase II clinical trial with the biotech industry.
Davunetide has previously shown efficacy in several Phase II clinical trials (i.e. in patients suffering from mild cognitive impairment, preceding Alzheimer's disease and in schizophrenia patients, protecting activities of daily living).
Publications
Bassan H, Kidron D, Bassan M, Rotstein M, Kariv N, Giladi E, Davidson A, Gozes I, Harel S. The effects of vascular intrauterine growth retardation on cortical astrocytes. J Matern Fetal Neonatal Med 23:595-600, 2010.
Fernandez-Montesinos R, Torres M, Baglietto-Vargas D, Gutierrez A, Gozes I, Vitorica J, Pozo D. Activity-dependent neuroprotective protein (ADNP) expression in the amyloid precursor protein/presenilin 1 mouse model of Alzheimer's disease. J Mol Neurosci 41:114-120, 2010.
Merenlender-Wagner A, Pikman R, Giladi E, Andrieux A, Gozes I. NAP (davunetide) enhances cognitive behavior in the STOP heterozygous mouse--a microtubule-deficient model of schizophrenia. Peptides 31:1368-1373, 2010. (Gozes I. recipient of Gayle A. Olson and Richard D. Olson prize for most meritorious original research article)
Shiryaev N, Jouroukhin Y, Gozes I. 3R tau expression modifies behavior in transgenic mice. J Neurosci Res 88:2727-2735, 2010.
Belokopytov M, Shulman S, Dubinsky G, Gozes I, Belkin M, Rosner M. Ameliorative effect of NAP on laser-induced retinal damage. Acta Ophthalmol 89:e126-131, 2011.
Dresner E, Agam G, Gozes I. Activity-dependent neuroprotective protein (ADNP) expression level is correlated with the expression of the sister protein ADNP2: deregulation in schizophrenia. Eur Neuropsychopharmacol 21:355-361.
Fleming SM, Mulligan CK, Richter F, Mortazavi F, Lemesre V, Frias C, Zhu C, Stewart A, Gozes I, Morimoto B, Chesselet MF. A pilot trial of the microtubule-interacting peptide (NAP) in mice overexpressing alpha-synuclein shows improvement in motor function and reduction of alpha-synuclein inclusions. Mol Cell Neurosci 46:597-606, 2011.
Sokolowska P, Passemard S, Mok A, Schwendimann L, Gozes I, Gressens P. Neuroprotective effects of NAP against excitotoxic brain damage in the newborn mice: implications for cerebral palsy. Neuroscience 173:156-168, 2011.
Idan-Feldman A, Schirer Y, Polyzoidou E, Touloumi O, Lagoudaki R, Grigoriadis NC, Gozes I. Davunetide (NAP) as a preventative treatment for central nervous system complications in a diabetes rat model. Neurobiol Dis. 44:327-339, 2011 (Cover Picture, December 2011 Issue).
Idan-Feldman, A., Ostritsky, R., and Gozes, I. Tau and caspase 3 as targets for neuroprotection. Int J Alzheimers Dis 493670, 2012.
Jouroukhin Y, Ostritsky R, Gozes I. D-NAP prophylactic treatment in the SOD mutant mouse model of amyotrophic lateral sclerosis: review of discovery and treatment of tauopathy. J Mol Neurosci 48:597-602, 2012.
Dresner E, Malishkevich A, Arviv C, Leibman Barak S, Alon S, Ofir R, Gothilf Y, I. Gozes I. Novel evolutionary-conserved role for the activity-dependent Neuroprotective Protein (ADNP) family That is important for erythropoiesis. J Biol Chem 287:40173-40185, 2012.
Oz S, Ivashko-Pachima Y, Gozes I. The ADNP derived peptide NAP modulates the tubulin pool: implication for neurotrophic and neuroprotective activities. PLoS One 7: e51458, 2012.
Jouroukhin Y, Ostritsky R, Assaf Y, Pelled G, Giladi E, Gozes I. NAP (davunetide) modifies disease progression in a mouse model of severe neurodegeneration: Protection against impairments in axonal transport. Neurobiol Dis. 56C:79-94, 2013.
Esteves AR, Gozes I, Cardoso SM. The rescue of microtubule-dependent traffic recovers mitochondrial function in Parkinson's disease. Biochim Biophys Acta. 1842:7-21, 2014.
Merenlender-Wagner A, Malishkevich A, Shemer Z, Udawela M, Gibbons A, Scarr E, Dean B, Levine J, Agam G, Gozes I. Autophagy has a key role in the pathophysiology of schizophrenia. Mol Psychiatry. 2013. doi: 10.1038/mp.2013.174
Gozes I, Schirer Y, Idan-Feldman A, David M, Furman-Assaf S. NAP alpha-aminoisobutyric acid (IsoNAP). J Mol Neurosci. 52:1-9, 2014
Schirer Y, Malishkevich A, Ophir Y, Lewis J, Giladi E, Gozes I. Novel marker for the onset of frontotemporal dementia: early increase in activity-dependent neuroprotective protein (ADNP) in the face of Tau mutation. PLoS One. 9:1, 2014
Gozes I, Iram T, Maryanovsky E, Arviv C, Rozenberg L, Schirer Y, Giladi E, Furman-Assaf S. Novel tubulin and TAU neuroprotective fragments sharing structural similarities with the drug candidate NAP (Davuentide). J Alzheimers Dis. 40 Suppl 1:S23-36.
Gozes I, Yeheskel A, Pasmanik-Chor M. activity-dependent neuroprotective protein (ADNP): a case study for highly conserved chordata-specific genes shaping the brain and mutated in cancer. J Alzheimers Dis. 2014 Nov 25. [Epub ahead of print].
Korolkov VV, Allen S, Roberts CJ, Gozes I, Tendler SJ. Study of NAP adsorption and assembly on the surface of HOPG. Peptides. 62:55-8. 2014.
Oz S, Kapitansky O, Ivashco-Pachima Y, Malishkevich A, Giladi E, Skalka N, Rosin-Arbesfeld R, Mittelman L, Segev O, Hirsch JA, Gozes I. The NAP motif of activity-dependent neuroprotective protein (ADNP) regulates dendritic spines through microtubule end binding proteins. Mol Psychiatry. 19:1115-24, 2014.
Boxer A, Lang AF, Grossman M, Knopman DS, Miller BL, Schneider LS, Doody RS, Lees A, Golbe L, Williams DR, Corvol J-C, Ludolph A, Burn D, Lorenzl S, Litvan I, Roberson ED, Koestler M, Jack CR Jr., Van Deerlin, V, Randolph C, Lobach IV, Gozes I, Whitaker S, Hirman J, Stewart AJ, Gold M, Morimoto BH on behalf of the AL-108-231 investigators. Davunetide for Progressive Supranuclear Palsy: a multicenter, randomized, double-blind, placebo controlled trial. Lancet Neurol. 13:676-85, 2014.
Merenlender-Wagner A, Shemer Z, Touloumi O, Lagoudakib R, Giladi E, Andrieux A, Grigoriadis NC, Gozes I. New horizons in schizophrenia treatment: Autophagy protection is coupled with behavioral improvements in a mouse model of schizophrenia. Autophagy. 2014 Nov 14:0. [Epub ahead of print]
Malishkevich A, Amram N, Hacohen-Kleiman G, Magen I, Giladi E, Gozes I. Activity-Dependent Neuroprotective Protein (ADNP) Exhibits Striking Sexual Dichotomy Impacting on Autistic and Alzheimer's Pathologies. Translational Psychiatry, in press.
Reviews
Gozes I. VIP-PACAP 2010: my own perspective on modulation of cognitive and emotional behavior. J Mol Neurosci 42:261-263, 2010.
Gozes I. Tau pathology and future therapeutics. Curr Alzheimer Res 7:685-696, 2010.
Gozes I. Davunetide (NAP) pharmacology: Neuroprotection and tau. In Emerging Drugs and Targets for Alzheimer's Disease. A. Martinez, editor. Cambridge: Royal Society of Chemistry. 108-128. 2010 (Book Chapter).
Gozes I. NAP (davunetide) provides functional and structural neuroprotection. Curr Pharm Des 17:1040-4. 2011.
Gozes I. Microtubules, schizophrenia and cognitive behavior: preclinical development of davunetide (NAP) as a peptide-drug candidate. Peptides 32:428-431, 2011.
Gozes I. Microtubules (tau) as an Emerging Therapeutic Target: NAP (Davunetide). Curr Pharm Des 17:1040-1044, 2011.
Shiryaev N, Pickman R, Giladi E, Gozes I. Protection against Tauopathy by the Drug Candidates NAP (Davunetide) and D-SAL: Biochemical, Cellular and Behavioral Aspects. Curr Pharm Des. 17:2603-2612, 2011.
Gold, M., Lorenzl, S., Stewart, A.J., Morimoto, B.H., Williams, D.R., and Gozes, I. Critical appraisal of the role of davunetide in the treatment of progressive supranuclear palsy. Neuropsychiatr Dis Treat 8:85-93, 2012.
Harmar, A.J., Fahrenkrug, J., Gozes, I., Laburthe, M., May, V., Pisegna, J.R., Vaudry, D., Vaudry, H., Waschek, J.A., and Said, S.I. Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1. Br J Pharmacol 166:4-17, 2012.
Gozes I. Neuropeptide GPCRs in neuroendocrinology: The case of Activity-Dependent Neuroprotective Protein (ADNP). Front. Endocrin. | doi: 10.3389/fendo.2012.00134.
Gozes I, Baas P. Activity-Dependent Neuroprotective Protein (ADNP) and Davunetide (NAP). In: Handbook of Biologically Active Peptides. Edited by Abba J. Kastin, Second Edition, Section XVIII, section editor: Illana Gozes (section pp. 1611-1653). Academic Press, pp. 1611-1618, 2013.
Oz S, Gozes I. The cytoskeleton as a pharmacological target. In: The Cytoskeleton, imaging, isolation and interaction R. Dermietzel, Editor). Neuromethods 79: 151-169, 2013.
Magen I, Gozes I. Microtubule-stabilizing peptides and small molecules protecting axonal transport and brain function: focus on davunetide (NAP). Neuropeptides. 47:489-95, 2013.
Magen I, Gozes I. Davunetide: peptide therapeutic in neurological disorders. Curr Med Chem. 21:2591-8, 2014.
A. Del Carmen Alonso, E. Elakkad, C. Gong, F Liu, T. Tanaka, T. Kudo, Y. Tatebayashi, J. Pei, J. Wang, S. Khatoon, M. Flory, B. Ghetti, I. Gozes, M. Novak, M. Novak, N.K. Robakis, M. de Leon, M. Iqbal. Inge Grundke-Iqbal, Ph.D. (1937-2012): The discoverer of the abnormal hyperphosphorylation of Tau in Alzheimer's Disease. J Mol Neurosci. 49: 430-435. 2013.
Gozes I. Journal of molecular neuroscience: impacting our brains. J Mol Neurosci. 54:291-2. 2014
Grants
2012-2015 Israeli Ministry of Science and Technology – New Models for ALS (with Rivka Ofir)
2014-2108 Israel Science Foundation - Deciphering beta-amyloid and tau neurotoxicity: Genome-wide RNA sequencing for sensitivity biomarkers- with Dr. David Gurwitz
