Besides intrinsic neuronal mechanisms and transneuronal propagation of the proteinopathy, the team posits that disease progression also relies on a complex pathological cell-cell interaction network.
The specific aims of the team are to better describe:
- How pathological protein assemblies (α-Syn and Tau) and other inflammatory cues shape microglial cell responses?
- How disease-associated brain vascular changes modulate neuroinflammation and clearance of pathological protein assemblies?
- How progressive dysfunction of non-DA neurotransmitter (NT) systems impacts on neurodegeneration and on immune cell polarization and function?
- How disease-relevant environmental factors impact PD pathogenesis?
- Mécharles S, Herrmann C, Poullain P, Tran TH, Deschamps N, Mathon G, Landais A, Breurec S, Lannuzel A. Acute myelitis due to Zika virus infection. Lancet. 2016 2; 387(10026):1481. (IF 44.00)
This article describes for the first time myelitis after Zika infection. The study was conducted to respond to a health emergency on the demand of Inserm and the French “Reacting network” to combat infectious diseases. It shows the reactivity of our team. This study was followed every week by Etienne Hirsch as part of his duties as Director of the Inserm Neuroscience, Neurology and Psychiatry Institute.
- Michel PP, Hirsch EC, Hunot S. Understanding Dopaminergic Cell Death Pathways in Parkinson Disease. Neuron. 2016 May 18; 90:675-91. (IF 13.97) This review article published in Neuron was chosen because it illustrates some of our work on cell death in Parkinson disease in the context of the published literature.
- Szelechowski M, Bétourné A, Monnet Y, Ferré CA, Thouard A, Foret C, Peyrin JM, Hunot S, Gonzalez- Dunia D. A viral peptide that targets mitochondria protects against neuronal degeneration in models of Parkinson’s disease. Nat Commun. 2014 Oct 21; 5:5181. (IF 11.32).
In this paper, we highlight the concept of mitochondrial filamentation as a neuroprotective strategy in PD.
This work led to patent application and was supported by ANR and Inserm Transfer grants.
- Belaid H, Adrien J, Laffrat E, Tandé D, Karachi C, Grabli D, Arnulf I, Clark SD, Drouot X, Hirsch EC, François C. Sleep disorders in Parkinsonian macaques: effects of L-dopa treatment andpedunculopontine nucleus lesion. J Neurosci. 2014 Jul 2; 34(27):9124-33. (IF 6.92)
This paper illustrates our work on the non-dopaminergic lesions in Parkinson disease. It shows the involvement of lesions of the pedunculopontine nucleus in sleep disorders after our previous work showing their role in gait and balance disorders.
- Sepulveda-Diaz JE, Ouidja MO, Socias SB, Hamadat S, Guerreiro S, Raisman-Vozari R, Michel PP. A simplified approach for efficient isolation of functional microglial cells: Application for modeling neuroinflammatory responses in vitro. Glia. 2016 Nov; 64(11):1912-24. (IF 5.99)
This paper provides a simplified approach for obtaining large yields of microglial cells for mechanistic studies or screening assays. The technique relies on the adhesion preference of microglial cells to the polycation polyethyleneimine.