Bases moléculaires, physiopathologie et traitement des maladies neurodégénératives

Leader

Co-Leaders

Research center

47 bld de l'Hôpital
75651 Paris
Alexis Brice

Institution

Inserm
CNRS
Université Pierre et Marie Curie
ED158
Université Pierre et Marie Curie

Laboratory

Phone: 01 57 27 46 82
Fax: 01 57 27 47 95
UMRS 1127 UMR 7225

Mots clefs

bases moléculaires
Physiopathologie
Parkinson
Alzheimer
Démences fronto-temporales
Ataxies cérébelleuses
Paraplégies spastiques et dystonies
 

publications

Depienne, C, et al. Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females. PLoS Genet, 5:e1000381, 2009.

Mochel, F, et al. Cerebellar ataxia with elevated cerebrospinal free sialic acid (CAFSA). Brain, 132:801-9, 2009.

Benajiba, L, et al. TARDBP mutations in motoneuron disease with frontotemporal lobar degeneration. Ann Neurol, 65:470-3, 2009.

Lesage, S, et al. Parkinson?s disease-related LRRK2 G2019S mutation results for independent mutational events in humans. HMG,19:1998-2004, 2010.

Slabicki, M, et al. A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic
paraplegia. PLOS-Biol, 8:e1000408, 2010.

Nalls, MA, et al. Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies. Lancet, 377:641-9, 2011.

Corvol, JC, et al. The COMT Val158Met polymorphism affects the response to entacapone in Parkinson's disease: a randomized crossover clinical trial. Ann Neurol, 69:111-8, 2011.

Depienne, C, et al. RAD51 haploisufficiency causes congenital mirror movements in humans. AJHG, 90:301-7, 2012.

Mochel, F, et al. Adult polyglucosan body disease: natural history and key MRI findings. Ann Neurol, 72:433-41, 2012.

Tesson, C, et al. Alteration of fatty-acid-metabolizing enzymes affects mitochondrial form and function in hereditary spasticparaplegia. AJHG, 91:1051-64, 2012.

Lee, Y-C, Dürr, A, et al. Mutations in KCND3 cause spinocerebellar ataxia type 22. Ann Neurol, 72:859-69, 2012.

Palminteri S, et al. Critical roles for anterior insula and dorsal striatum in punishment-based avoidance learning. Neuron, 76:998-1009,2012.

Martin, E, et al. Loss of function of glucocerebrosidase GBA2 is responsible for motor neuron defects in hereditary spastic paraplegia.AJHG, 92:238-44, 2013.

Chort, A, et al. Interferon-beta induces clearance of mutant ataxin-7 and improves locomotion in SCA7 knock-in mice. Brain,136:1732-45, 2013.

Depienne, C, et al. Brain white matter oedema due to ClC-2 chloride channel defi ciency: an observational analytical study. Lancet Neurol, 12:659-68, 2013.

Boukhris, A, et al. Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia. AJHG. 93:118-23,2013.

Lesage, S, et al. G51D alpha-synuclein mutation causes a novel parkinsonian-pyramidal syndrome. Ann Neurol, 73(4):459-71,2013.

Bertolin, G, et al. Parkin interacts with the TOM machinery to modulate mitochondrial protein import. Autophagy, 9(11):1-17,2013.

Esteves, T, et al. Loss of association of REEP2 with membranes leads to hereditary spastic paraplegia. AJGH, 94(2):268-77,2014.

van Rheenen W, et al. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis. Nat Genet. 2016 Sep;48(9):1043-8. doi: 10.1038/ng.3622. Epub 2016 Jul 25. 

Fields of research

Neurological and psychiatric diseases

Research Theme

Notre recherche est centrée sur l’étude des bases moléculaires et de la physiopathologie de différentes affections neurodégénératives. Les approches génétiques visent à cartographier des gènes responsables ou des facteurs de susceptibilité génétique de ces maladies (maladies de Parkinson et d’Alzheimer, démences fronto-temporales, ataxies cérébelleuses, paraplégies spastiques et dystonies). Ces avancées génétiques permettent d’établir la fréquence relative de chaque gène, son spectre mutationnel et d’établir des corrélations phénotype-génotype ainsi que d’identifier des biomarqueurs grâce au matériel biologique collecté à travers des réseaux nationaux et internationaux. Ce matériel inclut des données phénotypes précises et le cas échéant, le prélèvement biologique et tissulaire.

Lab rotation

Understanding vulnerability to mitochondrial dysfunction in Parkinson’s disease: a study in PINK1- and Parkin-deficient models

Chercheur responsable: 

BRICE Alexis

Dates: 

18 September 2017 - 29 June 2018

Date limite de candidature: 

29 June 2018

Period

~ Sept-Dec 2017 (to be discussed)

~ Jan-March 2018

~ April-June 2018

Project

PINK1 and Parkin, the functions of which are lost in familial Parkinson’s disease (PD) forms, are ubiquitous stress-responsive proteins that cooperate in the regulation of mitochondrial quality control. Our team explores the consequence of PINK1/Parkin dysfunction on the ability of neurons and glial cells to respond appropriately to stress. The student will participate in investigating how aberrant responses concur to trigger neuronal death through both cell autonomous and non-autonomous mechanisms. To this end, he/she will use a combination of techniques of cellular/molecular biology, biochemistry and microscopy in primary cells from knockout mice.

Contact

Institut du Cerveau et de la Moelle épinière - 47, boulevard de l’Hôpital 75013 Paris - +33 1 57 27 46 51 - olga.corti@icm-institute.org

Superviseur: 

CORTI Olga