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Séminaire - Etienne HirschUnmet therapeutic needs in Parkinson’s disease

Abstract :

Neurobiologiste, directeur de recherche au CNRS/ INSERM, spécialisé dans la maladie de Parkinson.

Parkinson’s disease is a neurodegenerative disorder characterize by a loss of dopaminergic neurons in the substantia nigra. The resulting symptoms are alleviated at early stages of the disease but when the disease progresses non dopaminergic lesions appear and the treatment is less efficient. Yet, the current treatments do not slow down the pathological process. Thus, the current unmet needs in Parkinson’s disease are the progression of neurodegeneration and the alleviation of the symptoms due to non-dopaminergic lesions.

The loss of dopaminergic neurons in Parkinson’s disease is due to mechanisms intrinsic to dopaminergic neurons involving accumulation of proteins such as α-synuclein, mitochondrial dysfunction, oxidative stress and apoptotic processes. Non cell autonomous mechanisms also participate to the cascade of events leading to the progression of neurodegeneration. In line with this, we recently showed that a CD4 lymphocyte infiltration is involved in neuronal degeneration in Parkinson’s disease by a Fas/Fas ligand mediated mechanism.

Non dopaminergic neurons also degenerate in Parkinson’s disease and especially cholinergic neurons projecting to the nigral dopaminergic neurons located in the pedunculopontine nucleus. In line with this we showed 1) that this region is involved in fast walking in healthy volunteers, 2) that it is lesioned in Parkinsonian patients with gait disorders and that a lesion of the cholinergic neurons in the pedunculopontine nucleus can produce gait disorders in animals. These data emphasize the role of non-dopaminergic lesion in Parkinson’s disease and their role gait disorders which represent one of the most debilitating symptom of the disease.

Selected publications

Hirsch, E., Graybiel, A.M., Agid, Y. Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease. Nature, 334, 345 348, 1988.

Anglade, P., Vyas, S., Javoy-Agid, F., Herrero, M.T., Michel, P.P., Marquez, J., Mouatt-Prigent, A., Ruberg, M., Hirsch, E.C., Agid, Y. - Apoptosis and autophagy in nigral neurons of patients with Parkinson's disease. Histol. and Histopathol., 12, 25-31, 1997. 

Damier, P., Hirsch, E.C., Agid, Y., Graybiel, A.M. – The substantia nigra of the human brain: II Patter
ns of loss of dopamine-containing neurons in Parkinson’s disease. Brain, 122, 1437-1448, 1999. 

Hartmann, Hirsch, E.C. et al.
Caspase-3: a vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease. Proc. Natl Acad. Sci., 97, 2875-2880, 2000.




Short Bio

Etienne Hirsch
Directeur de recherche au CNRS,


Directeur adjoint du CRICM (400 personnes) Centre de recherche de l’institut du cerveau et de la moelle épinière INSERM U975 CRICM, CNRS 7225,


Directeur de l’ITMO Neurosciences, Sciences cognitives, Neurologie et Psychiatrie

Prix de l’Académie de Science Grand Prix « Prix de la Fondation pour la recherche biomédicale - Prix François Lhermitte »,1999