Thérapeutique Expérimentale de la maladie de Parkinson

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: +33 (0) 1 57 27 45 57
UMRS 1127 UMR 7225
IHU AICM

Mots clefs

Neuroinflammation
Parkinson
neuronal death
physiopathology
experimental models
therapy
Cellular and Molecular Biology
 

publications

Karachi C, André A, Bertasi E, Bardinet E, Lehéricy S and Bernard F (2012) Functional parcellation of the lateral mesencephalus.JNeurosci. 32(27):9396-9401. (IF 7.27)ACL

Huynh MB, Villares J, Sepúlveda Díaz JE, Christiaans S, Carpentier G, Ouidja MO, Sissoeff L, Raisman-Vozari R, Papy-Garcia D (2012) Glycosaminoglycans from aged human hippocampus have altered capacities to regulate trophic factors activities but not A?42 peptide toxicity. Neurobiol Aging 33 (5), 1005.e11-22 (IF : 6.63)ACL

Dumurgier J, Crivello F, Mazoyer B, Tavernier B, Grabli D, François C, Tzourio-Mazoyer N, Tzourio C, Elbaz A (2012) Mri Atrophy Of The Caudate Nucleus And Slower Walking Speed In The Elderly: A Population-Based Study. Neuroimage 60 (2), 871-878(IF:5.94) ACL

Torres-Bugeau CM, Avila Cl, Raisman-Vozari R, Papy-Garcia D, Itri R, Barbosa Lr, Cortez Lm, Sim Vl, Chehin Rn (2012) Characterization of heparin-induced glyceraldehyde-3-phosphate dehydrogenase early amyloid-like oligomers and their implication on ?-synuclein aggregation. J Biol Chem 287: 2398-2409. (IF 5.33)ACL

Ribeiro N, Thuaud F, Bernard Y, Gaiddon C, Cresteil T, Hild A, Hirsch EC, Michel PP, Nebigil CG,Desaubry L (2012) Flavaglines as Potent Anticancer and Cytoprotective Agents. J Med Chem (IF 5.25) ACL

Fields of research

Neurological and psychiatric diseases

Research Theme

Notre projet vise deux objectifs complémentaires : 

1) Caractériser les mécanismes impliqués dans la progression de la mort neuronale dans les maladies neurodégénératives et en particulier la maladie de Parkinson ; 

2) Identifier les altérations fonctionnelles à l’origine des principaux symptômes de ces maladies. Notre objectif est centré sur les neurones dopaminergiques et cholinergiques qui sont préférentiellement lésés dans les syndromes parkinsoniens. Notre espoir est d’identifier des cibles thérapeutiques dans le but de ralentir la progression de la mort neuronale et de corriger les symptômes qui résultent d’une lésion non-dopaminergique. Ces deux aspects représentent encore des problèmes majeurs en termes de prise en charge des malades parkinsoniens. Les principales pistes poursuivies concernent : le stress oxydant, le rôle du calcium, de l’activité électrique et de la neuroinfllammation.

Etudiants ENP

Jaime FUENTEALBA

Lab rotation

Unravelling the role of perivascular macrophages in Parkinson’s disease pathophysiology

Chercheur responsable: 

HIRSCH Etienne

Dates: 

1 September 2016 - 31 December 2016

Date limite de candidature: 

1 September 2016

Lab Rotation:

~ Sep-Dec 2016 

Project:

Our central hypothesis is that perivascular macrophages (PVMs), an immune cell population strategically positioned within the perivascular space, may play a key role in PD pathophysiology by modulating neuro-immune responses and the fate/clearance of -Synuclein (-SYN) assemblies. This hypothesis is inspired by our pilot studies which indicate that PVM population is increased in postmortem tissue from PD patients. To address this question, we will first determine how PVMs dynamically respond to fully characterized α-SYN fibrils resulting in prion-like propagation of α-SYN aggregates and nigral dopaminergic (DN) degeneration. In a second task, we will evaluate the impact of cell-specific PVM depletion by brain delivery of clodronate liposomes, on neuropathological parameters including DN cell death, immune responses (local and leukocyte infiltration) and the spreading/clearance of α-SYN assemblies. We anticipate that PVM alteration in response to neurodegeneration will be associated with key mechanisms involved in disease progression.

Address: ICM 47 bd de l’Hôpital, Paris 13

Email : Stephane.hunot@upmc.fr  Phone: 0157274556 

Website

Superviseur: 

Stéphane HUNOT