Neurology

Pedro Gonzalez-Alegre, MD

Portrait

Specialty: Dystonia
Associate Professor of Neurology

Contact Information

Primary Office: 2100 RCP
Iowa City, IA 52242

Email: pedro-gonzalez-alegre@uiowa.edu
Web: Lab Website

Education

MD, University of Malaga Medical School, Malaga, Spain

Fellowship, Movement Disorders, University of Iowa Hospitals and Clinics, Iowa City, IA
Internship, St. Vincent Hospital, Worcester, MA
Residency, Neurology, University of Iowa Hospitals and Clinics, Iowa City, IA

Licensure and Certifications

Medical License, Iowa Board of Medical Examiners
Iowa Controlled Substance, DEA
ECFMG Certification, Educational Commission for Foreign Medical Graduates

Education/Training Program Affiliations

Biosciences Graduate Program
Interdisciplinary Graduate Program in Genetics
Interdisciplinary Graduate Program in Molecular and Cellular Biology
Interdisciplinary Graduate Program in Neuroscience
Medical Scientist Training Program

Research Summary

Dr. Gonzalez-Alegre's research aims to understand the biological basis of neurological disorders caused by dysfunction of the basal ganglia, and to develop novel therapies for this group of neurological diseases. Currently, studies focus on a disease known as DYT1 dystonia, the most common form of inherited dystonia. DYT1 dystonia, a dominantly inherited, incurable disease, is caused by a three-nucleotide deletion in the gene TOR1A that causes the loss of a glutamic acid in the protein torsinA, a AAA protein (ATPases Associated with diverse cellular Activities) that resides primarily in the endoplasmic reticulum. However, torsinA carrying the disease-causing mutation accumulates in the nuclear envelope. Analyses of dominant negative mutants suggest that torsinA normally functions within the perinuclear space of the nuclear envelope. In addition to torsinA, the mammalian torsin family of proteins includes torsinB, torsin-related protein 2A (torp2A) and torp3A. Over the next few years, my research will focus on DYT1 dystonia through three major projects: 1) Defining the biological role of torsinA in the nuclear envelope; 2) Characterize the expression and functional properties of the torsin gene family; 3) Development of therapeutic RNAi interference for DYT1 dystonia. Understanding the pathobiology underlying DYT1 dystonia could help us understand the biological basis for other forms of dystonia and the growing list of nuclear envelope-related human diseases, as well as reveal fundamental biological issues in nuclear envelope function and functional organization of the basal ganglia. In addition, these studies will contribute to exploit RNA interference as a therapy for DYT1 dystonia and other incurable neurological diseases.

Center, Program and Institute Affiliations

Center for Gene Therapy of Cystic Fibrosis and other Genetic Diseases

All Publications

Letort D, Gonzalez-Alegre P.  Huntington Disease in Children. Handbook of Neuropediatrics.  Handbook of Clinical Neurology, 3rd series.  2013. 113:1913-7.

Gordon K, Glenn K, Bode N, Wen H, Paulson H, Gonzalez-Alegre P.  The ubiquitin ligase F-box/G-domain protein 1 promotes the degradation of the disease-linked protein torsinA through the ubiquitin-proteasome pathway and macroautophagy.  Neuroscience.  2012 November. 224:160-71.
[PubMed]

Kakazu Y, Koh J, Iwabuchi S, Gonzalez-Alegre P, Harata N.  Miniature release events of glutamate from hippocampal neurons are influenced by the dystonia-associated protein torsinA..  Synapse (New York, N.Y.).  2012 September. 66(9):807-22.
[PubMed]

Byars J, Beglinger L, Moser D, Gonzalez-Alegre P, Nopoulos P.  Substance abuse may be a risk factor for earlier onset of Huntington disease..  Journal of neurology.  2012 September. 259(9):1824-31.
[PubMed]

Beglinger L, Prest L, Mills J, Paulsen J, Smith M, Gonzalez-Alegre P, Rowe K, Nopoulos P, Uc E.  Clinical predictors of driving status in Huntington's disease.  Movement disorders : official journal of the Movement Disorder Society.  2012 August. 27(9):1146-52.
[PubMed]

Kakazu Y, Koh J, Ho K, Gonzalez-Alegre P, Harata N.  Synaptic vesicle recycling is enhanced by torsinA that harbors the DYT1 dystonia mutation..  Synapse (New York, N.Y.).  2012 May. 66(5):453-64.
[PubMed]

Bode N, Massey C, Gonzalez-Alegre P.  DYT1 knock-in mice are not sensitized against mitochondrial complex-II inhibition..  PloS one.  2012. 7(8):e42644.
[PubMed]

Onwuameze O, McCormick L, Gonzalez-Alegre P, Beeghly J, Yasser K.  Maintenance ECT in a Patient with Multiple System Atrophy and Bipolar Disorder.  Journal of ECT (Electroconvulsive Therapy).  2012. 28(2):e1-2.

Strader S, Rodnitzky R, Gonzalez-Alegre P.  Secondary dystonia in a botulinum toxin clinic: clinical characteristics, neuroanatomical substrate and comparison with idiopathic dystonia..  Parkinsonism & related disorders.  2011 December. 17(10):749-52.
[PubMed]

Maric M, Shao J, Ryan R, Wong C, Gonzalez-Alegre P, Roller R.  A functional role for TorsinA in herpes simplex virus 1 nuclear egress..  Journal of virology.  2011 October. 85(19):9667-79.
[PubMed]

Martin J, Wolken N, Brown T, Dauer W, Ehrlich M, Gonzalez-Alegre P.  Lethal toxicity caused by expression of shRNA in the mouse striatum: implications for therapeutic design..  Gene therapy.  2011 July. 18(7):666-73.
[PubMed]

Gordon K, Glenn K, Gonzalez-Alegre P.  Exploring the influence of torsinA expression on protein quality control..  Neurochemical research.  2011 March. 36(3):452-9.
[PubMed]

Strader S, Rodnitzky R, Gonzalez-Alegre P.  Clinical and neuroanatomical characteristics of secondary dystonia..  63th Annual Meeting of the American Academy of Neurology.  2011. 

Bode N, Massey C, Gonzalez-Alegre P.  DYT1 knock in mice exhibit reduced toxicity by 3-nitropropionic acid..  5th International Dystonia Symposium.  2011. 

Wen H, Kim N, Fuentes E, Mallinger A, Gonzalez-Alegre P, Glenn K.  FBG1 is a promiscuous ubiquitin ligase that sequesters APC2 and causes S-phase arrest..  Cell cycle (Georgetown, Tex.).  2010 November. 9(22):4506-17.
[PubMed]

Glenn K, Wen H, Kim N, Mallinger A, Gonzalez-Alegre P.  A promiscuous ubiquitin ligase controls cell cycle through a unique mechanism. FASEB J. 24: lb151..  Experimental Biology Annual Meeting..  2010 April. 

Gonzalez-Alegre P.  Descriptions of cervical dystonia by Sir Charles Bell..  Movement disorders : official journal of the Movement Disorder Society.  2010 February. 25(3):257-9.
[PubMed]

Page M, Bao L, Andre P, Pelta-Heller J, Gonzalez-Alegre P, Bogush A, Khan L, Lacovitti L, Rice M, Ehrlich M.  Cell-autonomous alteration of dopaminergic transmission by wild type and mutant (delta E) TorsinA in transgenic mice.  Neurobiology of Disease.  2010. 39:318-326.

Gordon K, Bode N, Paulson H, Glenn K, Gonzalez-Alegre P.  Non-canonical degradation of torsinA by FBG ubiquitin ligases..  40th Annual Meeting of the Society for Neuroscience.  2010. 

Harris G, Dodelzon K, Gong L, Gonzalez-Alegre P, Paulson H.  Splice isoforms of the polyglutamine disease protein ataxin-3 exhibit similar enzymatic yet different aggregation properties..  PloS one.  2010. 5(10):e13695.
[PubMed]

Martin J, Wolken N, Brown T, Ehrlich M, Dauer W, Gonzalez-Alegre P.  Lethal striatal toxicity caused by shRNA expression in mouse models of DYT1 dystonia: implications for therapeutic design..  Keystone Symposia “RNA Silencing: Mechanism, Biology and Application”.  2010 January. 

Martin J, Bair T, Bode N, Dauer W, Gonzalez-Alegre P.  Transcriptional and proteomic profiling in a cellular model of DYT1 dystonia..  Neuroscience.  2009 December. 164(2):563-72.
[PubMed]

Harlow T, Gonzalez-Alegre P.  High prevalence of reported tremor in Klinefelter syndrome..  Parkinsonism & related disorders.  2009 June. 15(5):393-5.
[PubMed]

Gonzalez-Alegre P.  Solving the puzzle of dystonia..  Movements Disorders Society;  2009.  Available from: www.movementdisorders.org/monthly_edition/2009/02/puzzle_of_dystonia.php

Martin J, Wolken N, Brown T, Dauer W, Ehrlich M, Gonzalez-Alegre P.  Lethal toxicity caused by striatal delivery of shRNAs in mouse models of DYT1 dystonia: implications for therapeutic design..  12th Annual Meeting of the American Society for Gene Therapy.  2009. 

Gordon K, Gonzalez-Alegre P.  Consequences of the DYT1 mutation on torsinA oligomerization and degradation..  Neuroscience.  2008 December. 157(3):588-95.
[PubMed]

Bassuk A, Wallace R, Buhr A, Buller A, Afawi Z, Shimojo M, Miyata S, Chen S, Gonzalez-Alegre P, Griesbach H, Wu S, Nashelsky M, Vladar E, Antic D, Ferguson P, Cirak S, Voit T, Scott M, Axelrod J, Gurnett C, Daoud A, Kivity S, Neufeld M, Mazarib A, Straussberg R, Walid S, Korczyn A, Slusarski D, Berkovic S, El-Shanti H.  A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome..  American journal of human genetics.  2008 November. 83(5):572-81.
[PubMed]

Gonzalez-Alegre P.  Shooting the Messenger (RNA) in the Neurology Clinic: The Promise of Therapeutic RNA Interference..  AAN.com (webpage of the American Academy of Neurology), Science Editorials and Reviews.  2008 January 4. 
[Link]

Jinnah H, Richter A, Mink J, Caldwell G, Caldwell K, Gonzalez-Alegre P, Cookson M, Breakefield X, Delong M, Hess E.  Animal models for drug discovery in dystonia.  Expert Opinion on Drug Discovery.  2008. 3(1):83-97.

Gordon K, Gonzale-Alegre P.  Differences in torsinA degradation caused by the disease-linked mutation reveal potential therapeutic approaches for DYT1 dystonia..  38th Annual Meeting of the Society for Neuroscience.  2008. 

Gordon K, Bode N, Paulson H, Glenn K, Gonzalez-Alegre P.  Exploring torsinA degradation: potential role in DYT1 dystonia pathogenesis and therapeutics..  Gordon Research Conference “Autophagy In Stress, Development and Disease”.  2008. 

Harlow T, Rodnitzky R, Gonzalez-Alegre P.  From essential tremor to Klinefelter through fragile X, an unexpected journey.  Movement Disorders.  2008. 23(9):1328-1329.

Harlow T, Gonzalez-Alegre P.  High Prevalence of Tremor in Klinefelter Syndrome. .  60th Annual Meeting of the American Academy of Neurology.  2008. 

Harper S, Gonzalez-Alegre P.  Lentivirus-mediated RNA interference in Mammalian neurons.  Methods in Molecular Biology.  2008. 442:95-112.

Gonzalez-Alegre P.  Therapeutic RNA interference for neurodegenerative diseases.  Revista de neurologia.  2008. 47(12):641-7.
[PubMed]

Gonzalez-Alegre P, Paulson H.  Technology insight: therapeutic RNA interference--how far from the neurology clinic?.  Nature clinical practice. Neurology.  2007 July. 3(7):394-404.
[PubMed]

Gonzalez-Alegre P.  Monomelic parkinsonian tremor caused by contralateral substantia nigra stroke..  Parkinsonism & related disorders.  2007 April. 13(3):182-4.
[PubMed]

Gonzalez-Alegre P.  The inherited dystonias..  Seminars in neurology.  2007 April. 27(2):151-8.
[PubMed]

Gonzalez-Alegre P.  Therapeutic RNA interference for neurodegenerative diseases: From promise to progress..  Pharmacology & therapeutics.  2007 April. 114(1):34-55.
[PubMed]

Martin J, Gonzalez-Alegre P.  Gene expression profiling in a cellular model of DYT1 dystonia..  37th Annual Meeting of the Society for Neuroscience.  2007. 

Gordon K, Gonzalez-Alegre P.  TorsinA is degraded both by the proteasome and macroautophagy..  37th Annual Meeting of the Society for Neuroscience.  2007. 

Gonzalez-Alegre P, Kelkar P, Rodnitzky R.  Isolated high-frequency jaw tremor relieved by botulinum toxin injections..  Movement disorders : official journal of the Movement Disorder Society.  2006 July. 21(7):1049-50.
[PubMed]

Gonzalez-Alegre P, Afifi A.  Clinical characteristics of childhood-onset (juvenile) Huntington disease: report of 12 patients and review of the literature..  Journal of child neurology.  2006 March. 21(3):223-9.
[PubMed]

Rodriguez-Lebron E, Gonzalez-Alegre P.  Silencing neurodegenerative disease: bringing RNA interference to the clinic..  Expert review of neurotherapeutics.  2006 February. 6(2):223-33.
[PubMed]

Jinnah H, Visser J, Harris J, Verdu A, Larovere L, Ceballos-Picot I, Gonzalez-Alegre P, Neychev V, Torres R, Dulac O, Desguerre I, Schretlen D, Robey K, Barabas G, Bloem B, Nyhan W, Kremer R, Eddey G, Puig J, Reich S.  Delineation of the Motor Disorder of Lesch-Nyhan Disease.  Brain.  2006. 129:1201-1217.
[PubMed]

Smith H, Anderson S, Gonzalez-Alegre P.  Heterogeneity of MMPI-2 abnormalities in patients with psychogenic movement disorders suggests the need for diverse therapeutic approaches..  58th Annual Meeting of the American Academy of Neurology.  2006. 

Paulson H, Gonzalez-Alegre P.  RNAi gets its prize..  The Lancet Neurology.  2006. 5(12):997-999.

Miller V, Paulson H, Gonzalez-Alegre P.  RNA interference in neuroscience: progress and challenges..  Cellular and molecular neurobiology.  2005 December. 25(8):1195-207.
[PubMed]

Gonzalez-Alegre P, Bode N, Davidson B, Paulson H.  Silencing primary dystonia: lentiviral-mediated RNA interference therapy for DYT1 dystonia..  The Journal of neuroscience : the official journal of the Society for Neuroscience.  2005 November. 25(45):10502-9.
[PubMed]

Gonzalez-Alegre P.  Severe interscapular pain and increased creatine kinase activity: the answer was in the ankles..  Emergency medicine journal : EMJ.  2005 February. 22(2):152-3.
[PubMed]

Gonzalez-Alegre P, Rodriguez-Lebron E, Bode N, Davidson B, Paulson H.  Development of a therapeutic RNAi lentivirus for DYT1 dystonia..  35th Annual Meeting of the Society for Neuroscience.  2005. 

Gonzalez-Alegre P, Paulson H.  Aberrant cellular behavior of mutant torsinA implicates nuclear envelope dysfunction in DYT1 dystonia..  The Journal of neuroscience : the official journal of the Society for Neuroscience.  2004 March. 24(11):2593-601.
[PubMed]

Gonzalez-Alegre P, Paulson H.  Aberrant cellular behavior of mutant TorsinA implicates nuclear envelope dysfunction in DYT1 dystonia..  8th International Congress of Parkinson’s Disease and Movement Disorders.  2004. 

Gonzalez-Alegre P, Ammache Z, Davis P, Rodnitzky R.  Moyamoya-induced paroxysmal dyskinesia..  Movement disorders : official journal of the Movement Disorder Society.  2003 September. 18(9):1051-6.
[PubMed]

Gonzalez-Alegre P, Miller V, Davidson B, Paulson H.  Toward therapy for DYT1 dystonia: allele-specific silencing of mutant TorsinA..  Annals of neurology.  2003 June. 53(6):781-7.
[PubMed]

Gonzalez-Alegre P, Miller V, Davidson B, Paulson H.  oward therapy for DYT1 dystonia: Allele-specific silencing of mutant torsinA..  55th Annual Meeting of the American Academy of Neurology.  2003. 

Gonzalez-Alegre P, Tippin J.  Prolonged cortical electrical depression and diffuse vasospasm without ischemia in a case of severe hemiplegic migraine during pregnancy..  Headache.  2003 January. 43(1):72-5.
[PubMed]

Gonzalez-Alegre P, Ammache Z, Davis P.  Clinical characteristics and outcome of adult moyamoya disease in an American population..  54th Annual Meeting of the American Academy of Neurology..  2002. 

Gonzalez-Alegre P, Recober A, Kelkar P.  Idiopathic brachial neuritis..  The Iowa orthopaedic journal.  2002. 22:81-5.
[PubMed]

Bonansco C, Gonzalez de la Vega A, Gonzalez-Alegre P, Borde M, Garcia-Segura L, Buno W.  Tetanic stimulation of Schaffer collaterals induces rhythmic bursts via NMDA receptor activation in rat CA1 pyramidal neurons.  Hippocampus.  2002. 12:434-446.

Gonzalez-Alegre P, Ruiz-Lopez A, Abarca-Costalago M, Gonzalez-Santos P.  Increment of the platelet count in temporal arteritis: response to therapy and ischemic complications.  European Journal of Neurology.  2001. 45(1):43-45.

Sanchez-Chaparro M, Merida de la Torre F, Gonzalez-Alegre P, Gonzalez-Santos P.  Transverse myelitis caused by Brucella.  Revista Clínica Española.  1999 November. 199(11):778.

Gonzalez-Alegre P, Abarca-Costalago M, Ruiz-Lopez A, Fernandez-Nebro A, Haro-Liger M, Palacios-Munoz R, Gonzalez-Santos P.  Comparative study between giant cell arteritis and polymyalgia rheumatica.  XXX Congress of the Internal Medicine Society of Spain..  1998. 

Gonzalez-Alegre P, Abarca-Costalago M, Ruiz-Lopez A, Fernandez-Nebro A, Rodriguez-Andreu J, Palacios-Munoz R, Gonzalez-Santos P,  .  Giant cell arteritis. Descriptive study of 42 patients..  XXX Congress of the Internal Medicine Society of Spain. .  1998. 

Buno W, Bonansco C, Gonzalez-Alegre P, Gonzalez de la Vega A, Garcia-Segura L.  Theta-like membrane potential oscillations induced by NMDA-receptor activation in CA-1 pyramidal cells in vitro..  28th Annual Meeting of the Society for Neuroscience..  1998. 

Ruiz-Lopez A, Gonzalez-Alegre P, Abarca-Costalago M, Rodriguez-Andreu J, Haro-Liger M, Garcia-Cortes M, Gonzalez-Santos P.  Thrombocytosis and ischemic complications in giant cell arteritis..  XXX Congress of the Internal Medicine Society of Spain.  1998. 

Lopez de Miguel M, Gonzalez-Alegre P, Lara J, Dawid-Milner M, Gonzalez-Baron S.  A5 modulation of cardiorespiratory responses to parabrachial stimulation in the anaesthetized rat..  International Joint Meeting of Physiology. Sociedad Española de Ciencias Fisiológicas and The American Physiological Society. J Physiol Biochem. (Rev Esp Fisiol.).  1997. 53(1):69.

Gonzalez-Baron S, Lopez de Miguel M, Gonzalez-Alegre P, Lara J, Dawid-Milner M.  A5 pontine region modulates the parabrachial expiratory and pressor responses in the anaesthetized rat..  27th Annual Meeting of the Society for Neuroscience..  1997. 

Buno W, Bonansco C, Gonzalez-Alegre P, Gonzalez de la Vega A, Garcia-Segura L.  Intrinsic theta-like membrane potential oscillations induced by NMDA-receptor activation in CA1 pyramidal cells in vitro..  5th Mediterranean Epilepsy Conference. 1st Mediterranean Neuroscience Conference. .  1997. 

Lopez de Miguel M, Gonzalez-Alegre P, Lara J, Dawid-Milner M, Gonzalez-Baron S.  Modulacion de la respuesta cardiorrespiratoria del grupo respiratorio protuberancial por el area A5 pontina. .  VII Congreso de la Sociedad Española de Neurociencia. .  1997. 

Gonzalez-Alegre P, Buffard V, Wang K, Henien S, Morcuende J.  Exploring the link between dystonia genes and idiopathic scoliosis.  Journal of Pediatric Orthopaedics. 

Gonzalez-Alegre P.  RNA interference (2010).  Encyclopedia of Movement Disorders. Oxford: Academic Press; 

Date Last Modified: 08/27/2013 - 09:39:38