SOD1 intracellular localization in copper-depleted NSC-34

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SOD1 intracellular localization in copper-depleted NSC-34

    Mutant SOD1 and familial ALS:

     from the molecule to man

    Milan (Italy) September 13-16, 2007

    MARIO NEGRI Institute


    Caterina Bendotti;

    Maria Teresa Carrì;

    Alberto Ferri;

    Lavinia Cantoni;

    Scientific Committee

    Caterina Bendotti

    Maria Teresa Carrì

    Stefan L. Marklund

    Giuseppe Rotilio

    Pamela Shaw

    Joan S. Valentine


    Annalisa Volpe;

Dear Colleagues and Friends,

    It is a great pleasure for us to welcome you to this first meeting on mutant SOD1 and familial ALS in Milano, Italy.

    The conference is focussed on the selective neurotoxic properties of mutant SOD1, from biochemical and biophysical data in vitro to results in vivo from studies in animal models and patients. Hopefully, this meeting will offer the opportunity to review and discuss existing evidence and new hypotheses on the mechanisms of mutant SOD1-linked ALS, and encourage scientific collaboration. We are certain that this will be of help both to all the neuroscientists already working in the field and to those that are now joining in the attempt to understand the cause of this rather obscure disease.

    Since the conference is running in Milano, we are also pleased to be able to offer you the exclusive opportunity to visit the famous “Last Supper” painted by Leonardo da Vinci from 1495 to 1498.

    We wish to thank all participants, all the people who have assisted us in the organization of the meeting and our sponsors that made it possible.

    Last, but not least, many thanks are due to Prof. Silvio Garattini, director of the Mario Negri Institute, for kindly hosting the meeting.

     Caterina Bendotti Maria Teresa Carrì


    Scientific Program

Thursday 13 September

Registration 3.30 pm

Welcome Ceremony 5.30 pm

    Caterina Bendotti, Maria Teresa Carrì

    Silvio Garattini ( Director of Mario Negri Institute) Mario Melazzini ( President of AISLA)

Opening lecture 6.00 pm

    S1 - Giuseppe Rotilio (Italy)

    From erythrocuprein to SOD1: memories of a Biochemist.

Welcome party 7.00 pm

Friday 14 September

Session I 8.30 am 10.45 am

    Biochemistry of Mutant SOD1s

    Chairpersons: J.S. Valentine G. Rotilio

S2 - Joan S. Valentine (USA)

    How do ALS-associated mutations in superoxide dismutase 1 promote aggregation

    of the protein?

S3 - Mikael Oliveberg (Sweden)

    ALS-associated SOD1 mutations preferentially reduce the proteins repulsive charge

S4 - Lucia Banci (Italy)

    Interplay between structural and dynamical properties and protein aggregation in


S5 - Joseph S. Beckman (USA)

    Direct measurement of zinc-deficient SOD localized the ventral gray matter in G93A

    SOD rats

Selected oral communication

    SO1 - Albrecht Clement (Germany)

    Dismutase-inactive mutant SOD1 has different functional properties when

    heterodimerized with wild type SOD1

Coffee break (10.45 am -11.15 am)


Session II 11.15 am 1.00 pm

    Mutant SOD1s toxicity in cell models

    Chairpersons: S.L. Marklund M.T. Carrì

S6 - Pamela Shaw (UK)

    Mutant SOD1 in motoneuronal cells: mechanisms from the genomic and proteomic


S7 - Gen Sobue (Japan)

    Mutant SOD1s and protein aggregation/degradation in motoneuronal cells

S8 - Maria Teresa Carrì (Italy)

    Mutant SOD1s and mitochondria in motoneuronal cells

Selected oral communication

    SO2 - Mauro Cozzolino (Italy)

    Cysteine 111 affects aggregation of mutant SOD1 in NSC34 cells

Lunch (1.00 pm 2.00 pm)

Session III 2.00 pm 4.15 pm

    Mutant SOD1s toxicity in animal models

    Chairpersons: Z.S. Xu W. Robberecht

S9 - Stefan L. Marklund (Sweden)

    Soluble misfolded SOD1 species in ALS

S10 - Jean-Pierre Julien (Canada)

    From secretion of SOD1 mutants to immunotherapeutic approaches

S11 - Jasna Kriz (Canada)

    Live imaging of disease progression in SOD1 mutant mice

S12 - Valentina Bonetto (Italy)

    Proteomics of spinal cord aggregates in G93A SOD1 transgenic mouse

Selected oral communication

    SO3 - Avi Chakrabartty (Canada)

    Detection of misfolded SOD1 in sporadic and familial ALS

Coffee break (4.15 pm 4.45 pm)


Session IV 4.45 pm 6.45 pm

    Genetics of Familial ALS

    Chairpersons: C.E. Shaw A. Chiò

S13 - Peter M. Andersen (Sweden)

    Genetics of SOD1-linked fALS

S14 - Christopher E. Shaw (UK)

    Genetics of non-SOD1-linked fALS

S15 - Stefania Battistini (Italy)

    SOD1 in Italian ALS patients

S16 - Wim Robberecht

    The pathogenesis of sporadic amyotrophic lateral sclerosis

Selected oral communication

    SO4 - Richard Wroe (UK)

    The Evolution of the Amyotrophic Lateral Sclerosis Database (ALSOD)

Social Event - Visit to Leonardo’s “Last Supper” 7.30 pm

    Social Dinner 8.30 pm

Saturday 15 September

Session V 8.30 am 10.15 am

    Motor neuron death in SOD1-linked fALS: intra-cellular mechanisms

    Chairpersons: L. Cantoni P. Pasinelli

S17 - Piera Pasinelli (USA)

    The double life of two pro-survival proteins: when SOD1 and Bcl-2 get mutated, wild

    and pro-death

S18 - Claudia Crosio (Italy)

    Role of Bcl2a1 in SOD1-linked fALS

S19 - Angelo Poletti (Italy)

    The nucleus as target for mSOD1 toxicity

S20 - Massimo Tortarolo (Italy)

    Role of MAP kinases cascade in SOD1-linked fALS

Selected oral communication

    SO5 - Haining Zhu (USA)

    Interaction between familial ALS-linked SOD1 mutants and the dynein complex


Coffee break (10.15 am 10.45 am)

Session VI 10.45 am 12.30 noon

    Motor neuron death in SOD1-linked fALS: inter-cellular mechanisms Chairpersons: M. Bentivoglio L. Barbeito

S21 - Luis Barbeito (Uruguay)

    SOD1 mutations and astrocyte dysfunction in ALS

S22 - Marina Bentivoglio (Italy)

    Neuroinflammatory signalling in the motor circuit in SOD1-linked fALS

S23 - Davide Trotti (USA)

    Post-translational processing of the glial glutamate transporter EAAT2 in ALS

Selected oral communication

    SO7 - Giambattista Bonanno (Italy)

    Excessive exocytotic release of glutamate in the spinal cord of SOD1 G93A mutant


Lunch (12.30 noon 1:30 pm)

Session VII 1:30 pm 3.15 pm

    Motor neuron death in SOD1-linked fALS: remote contributions Chairpersons: J.P.Loeffler A.Musarò

S24 - Antonio Musarò (Italy)

    Muscle control of motor neuron survival and activity

S25 - Linda Greensmith (UK)

    Axonal Transport deficits in models of motor neuron disease

S26 - Jean-Philippe Loeffler (France)

    Energy homeostasis and denervation processes at the neuro-muscular junction in ALS

Selected oral communication

    SO8 - Valeria Padovano (Italy)

    Effects of physical exercise and the steroid nandrolone on neuromuscular junctions

    in G93A -SOD1 transgenic mice

Coffee break (3.15 pm 3.45 pm)

Session VIII 3.45 pm 5.45 pm

    Poster Session


Sunday 16 September

Session IX 8.30 am 12.30 noon

    Therapeutics in SOD1 mutant mice

    Chairpersons: V. Silani C. Raoul

S27 - Cedric Raoul (Switzerland)

    Lentiviral and adeno-associated viral vectors for motoneuron gene therapy

S28 - Zuoshang Xu (USA)

    An RNAi approach to understanding the mechanism and therapy of ALS caused by mutant SOD1

S29 - Vincenzo Silani (Italy)

    Translational research: possible explanations for the failure in ALS

Coffee break (10.00 am -10.30 am)

S30 - Jonathan Glass (USA)

    SOD1-People: It's time for a trial

S31 - Lucie Bruijn (USA)

    Drug discovery and development for ALS

Selected oral communication

    SO9 - Rita Perlingeiro (USA)

    The potential of endothelial progenitors to recover the stem cell niche in ALS

Closing remarks

    Caterina Bendotti (Italy)


Individual departure (Sandwiches available)


Invited Lectures



From erythrocuprein to SOD-1: memories of a Biochemist

Giuseppe Rotilio

Department of Biology, “Tor Vergata” University of Rome. Italy

    Recollecting steps of his lifelong experience over decades of biochemical research on Cu,Zn SOD, the author will touch upon some findings obtained in the Rome laboratory, which scan the evergreen primacy of this green protein on different stages of biochemistry, even with changing pen names.

    Born as a humble vehicle for copper in blood and tissues (erythrocuprein), grown up unexpectedly to an unrivalled leading role as superfast enzyme, top model for metalbinding protein centres and

    primary defence against ROS (superoxide dismutase), then rejuvenated in the play of metal traffic in the cell (cytocuprein), it is presently recognized as an invaluable key to understand biochemical mechanisms of life, death and disease (SOD 1).



    How do ALS-associated mutations in superoxide dismutase 1 promote aggregation of the protein?

    Joan Selverstone Valentine

    Department of Chemistry and Biochemistry, UCLA, Los Angeles, California 90095-1569, USA.

    More than 100 different mutations in the gene encoding copper-zinc superoxide dismutase (SOD1) cause familial forms of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease in which aggregation of the SOD1 protein is widely believed to be the primary mode of pathogenesis. We have studied the mutant SOD1 proteins using two different approaches: characterization of expressed and purified protein and analysis of SOD1 in transgenic mouse spinal cords. In vitro,

    mutant SOD1 proteins show remarkably diverse structures, activities and native state stabilities. Some of the mutations cause enormous changes while others seem to have no measurable effect on its biophysical and biochemical properties. To address the question of how such widely differing proteins can all cause the same disease, we have turned to analysis of the SOD1 aggregates isolated from the spinal cords of transgenic ALS mice. Analysis of spinal cords from three different strains of ALS-SOD1 mutant mice by mass spectrometric and shotgun-proteomic methods revealed that the SOD1 proteins that are recovered from the isolated aggregates are predominantly the full-length SOD1 polypeptide. The recovered SOD1 proteins did not bear post-translational modifications such as ubiquitination, carboxymethylation, or extensive oxidation. The aggregates were composed almost entirely of SOD1, although various proteins that are highly abundant in spinal tissue were found in very low amounts, along with SOD1. The significance of these findings for ALS will be discussed.


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