Experimental therapeutics of Parkinson disease

Leader

Etienne
HIRSCH

Co-Leaders

Stéphane
HUNOT

Research center

Institut du Cerveau et de la Moelle épinière
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
Website
IHU AICM

Keywords

Neuroinflammation
Parkinson
physiopathology
experimental models
Cellular and Molecular Biology
therapy
 

Publications

Rousseau E, Michel PP, Hirsch EC. The iron-binding protein lactoferrin protects vulnerable dopamine neurons from degeneration by preserving mitochondrial calcium homeostasis. Mol Pharmacol. 2013 Dec;84(6):888-98. doi: 10.1124/mol.113.087965. Epub 2013 Sep 27.

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

Our project is driven by two major complementary objectives:

1) to characterize the mechanisms involved in the progression of nerve cell death in neurodegenerative disorders and especially Parkinson’s disease (PD);

2) to identify functional alterations underlying key clinical symptoms in these disorders. To that aim, we concentrate on the populations of dopaminergic (DA) and cholinergic neurons that are preferentially affected in PD. Our hope is to identify therapeutic targets to slow the progression of neuronal loss and to alleviate symptoms originating from non-DA lesions which represent two major unmet needs for patients suffering from PD. The main targets analyzed are oxidative stress, the role of calcium homeostasis, electrical activity and neuroinflammatory processes.

ENP Students

Jaime FUENTEALBA

Lab rotation

Pathological spreading of patient-derived Synuclein fibrils in mouse

Team leader: 

HIRSCH Etienne

Dates: 

September 18, 2017 - December 23, 2017

Application deadline: 

June 29, 2018

Period

~ Sept-Dec 2017

Project

Our working hypothesis is that alpha-synuclein (SYN) assemblies with different structural characteristics or ‘strains’ display distinct spreading, tropism, clearance and neurotoxicity. The goal of the project is to test in vivo (mouse) the pathological spreading capacity of different fibrillary SYN assemblies obtained by protein misfolding cyclic amplification (PMCA) of patient-derived brain aggregates (PD, MSA, DLB). Technics such as stereotaxic brain injections, immunohistochemistry and image analysis will be employed.

Contact

Institut du Cerveau et de la Moelle épinière - 47, boulevard de l'Hôpital 75013 Paris - +33 1 57 27 45 56 - Stephane.hunot@upmc.fr

Supervisor: 

HUNOT Stéphane