GROUP 1: Metabolic impacts in tauopathies

About

Understanding the molecular mechanisms of brain ageing and neurodegenerative diseases remains a major challenge in the context of increasing life expectancy. The balance between healthy and pathological ageing depends on multiple factors and the early stages of disruption of this balance are a key point for understanding the molecular basis of neurodegenerative diseases, such as Alzheimer's or Parkinson's, in order to propose new diagnostics and treatments.

The team's strategy is to:

(1) model neurodegenerative diseases and create innovative models by inducing pathology through gene transfer or induction of inflammation and thus increase the potential of the mouse lemur model, a natural model of age-related amyloidopathy. The team is historically involved in a better characterization of the ageing Microcebus. Our studies use different approaches from genetics, transcriptomics, viral transgenesis, histology, microfluidics... to brain magnetic resonance imaging (MRI) and behavioral and cognitive studies. Finally, we are developing, from biopsies, various cellular models (fibroblasts, neurons, etc.) which we use to explore new molecular signaling pathways or test new therapeutic targets.

(2) to establish potential biomarkers to target the pathological heterogeneity of neurodegenerative diseases by focusing on the Reg-1α protein, using a multidisciplinary approach ranging from cellular studies to in vivo approaches (zebrafish, rodents, non-human primates). Reg-1α is an inflammatory protein found both aggregated in the brains of Alzheimer's disease patients, and capable of stimulating hyperphosphorylation of the Tau protein, in models of tauopathies. Currently, we are dissecting the molecular mechanisms linking Reg-1α to the lesions characteristic of tauopathies, focusing in particular on the impact of metabolic or inflammatory risk factors in this dialogue.

(3) Study of Ca2+ signaling and its homeostasis in neurons and neural stem cells of different species, under normal and pathophysiological conditions.

(4) We are also developing an epidemiological line of research aimed at better identifying, in humans, the role of lifestyle and metabolic factors in brain ageing processes.

Group

Nadine Mestre-Francés, group leader

snadine

Study Director EPHE

Contact: nadine.frances(at)umontpellier.fr

Phone: 04 67 14 42 52

Govindan Dayanithi

daya

Research director CNRS

Contact: govindan.dayanithi(at)umontpellier.fr

Jean-Michel Verdier

verdier

Study Director EPHE

Contact: jean-michel.verdier(at)ephe.psl.eu

Phone: 04 67 14 33 86

Jean-Marie Robine

robine

Demographer, Emeritus Research Director, Inserm, and Professor at EPHE
Cermes3 et MMDN (U1198), Associate researcher at INED (MSE)

Contact: jean-marie.robine(at)inserm.fr

Phone : 04 67 14 33 85

Christelle Lasbleiz

lasbleiz

Lecturer EPHE

Contact: christelle.lasbleiz(at)umontpellier.fr

Phone : 04 67 14 93 47

Marie-Christine Lebart

lebart

Lecturer, EPHE

Contact: marie-christine.lebart(at)umontpellier.fr

Phone: 04 67 14 38 89

Françoise Trousse

trousse

Lecturer EPHE

Contact: francoise.trousse(at)umontpellier.fr / francoise.trousse(at)ephe.sorbonne.fr

Phone: 04 67 14 48 30

Anne Marcilhac

marcilhac

Lecturer, EPHE

Contact: anne.marcilhac(at)umontpellier.fr

Phone: 04 67 14 48 30

Pascaline Fontès

fontes

Assitant Engineer, Université de Montpellier

Contact: pascaline.fontes(at)umontpellier.fr 

Phone: 04 67 14 42 52

Joel Cuoq

silhouette h

Technician EPHE

Contact: joel.cuoq(at)umontpellier.fr

Phone: 04 67 14 33 87

Faustine Hugon

silhouette f

Technical assistant EPHE

Contact: fausthugon(at)gmail.com

Phone: 04 67 14 33 87

Cléa Vincent

vincent

Technician CDD UM

Contact: clea.vincent(at)umontpellier.fr

Phone: 04 67 14 42 52

Meline Peguet

silhouette f

Technical assistant EPHE, CDD

Contact:

Phone:

Sam Hana

hana

PhD Student

Contact:

Phone:

References

  • Schmidtke D, Zimmermann E, Trouche SG, Fontès P, Verdier JM, Mestre-Francés N. Linking cognition to age and amyloid-β burden in the brain of a nonhuman primate (Microcebus murinus). Neurobiol Aging. 2020 Oct;94:207-216. doi: 10.1016. PMID: 32650184.
  • Varilh M, Acquatella-Tran Van Ba I, Silhol M, Nieto-Lopez F, Moussaed M, Lebart MC, Bovolenta P, Verdier JM, Rossel M, Marcilhac A, Trousse F. Reg-1α Promotes Differentiation of Cortical Progenitors via Its N-Terminal Active Domain. Front Cell Dev Biol. 2020 Aug 13;8:681. doi: 10.3389/fcell.2020.0068.
  • Moussaed M, Huc-Brandt S, Cubedo N, Silhol M, Murat S, Lebart MC, Kovacs G, Verdier JM, Trousse F, Rossel M, Marcilhac A. Regenerating islet-derived 1α (REG-1α) protein increases tau phosphorylation in cell and animal models of tauopathies. Neurobiol Dis. 2018 Nov;119:136-148. doi: 10.1016 PMID: 30092268.
  • Trousse F, Jemli A, Silhol M, Garrido E, Crouzier L, Naert G, Maurice T, Rossel M (2019) Knockdown of CXCL12 /CXCR7 chemokine pathway results in learning deficits and neural progenitors maturation failure in mice. Brain Behav Immun. 80: 697-710.
  • Mestre-Francés N, Serratrice N, Gennetier A, Devau G, Cobo S, Trouche SG, Fontès P, Zussy C, De Deurwaerdere P, Salinas S, Mennechet FDJ, Dusonchet J, Schneider BL, Saggio I, Kalatzis V, Luquin-Piudo MR, Verdier JM, Kremer EJ (2018) Exogenous LRRK2G2019Sinduces parkinsonian-like pathology in a nonhuman primate. JCI Insight 3 (14):e98202.