L'Institut de NeuroPhysiopathologie (INP) est un centre d'excellence pour la formation et la recherche qui allie la recherche fondamentale et translationnelle pour étudier l'organisation, la fonction et l'interaction des cellules neurales, les bases moléculaires et cellulaires des principales maladies du cerveau, et développer des stratégies de thérapies cellulaires et moléculaires innovantes.
Equipes de recherche
Plateforme NeuroTimone (PFNT)
La PFNT (Plateforme NeuroTimone) est un ensemble cohérent d'outils d'exploration en neurobiologie permettant des investigations aux échelles moléculaires, cellulaires et intégrées.
A la Une
-
Chiara received a prize for the best master’s thesisCongratulations to Chiara Bordier (team 2 SynapTau) for receiving the GBM (Association for Biochemistry and Molecular Biology) Master Prize for the best master’s thesis! This year, Professor Lichtenthaler from Technische Universität München and the DZNE presented this honour, marking the fourth time it has been awarded. Chiara's award-winning research explored the impact of Tau protein on nuclear organization and chromatin dynamics in neurodegenerative diseases, highlighting its crucial role in nuclear tension and stress response.
-
INP & VH invited to the "Imagining the futur of cancer treatments" symposiumINP and Vect-Horus both participated to the symposium “Imagining the future of cancer treatments” (~100 participants) organized by the Translate-It departement of CRCM in Luminy. Along with keynote speaker Maria Kavallaris (Director of the Australian Centre for NanoMedicine at UNSW), François Devred gave an overview of INP's work on cancer entitle "How the INP contributes to the future of cancer treatments" and Pavlo Shpak-Kraievskyi of Vect-Horus gave a talk on "Surface modification of LNPs for brain targeting of nucleic acids".
-
3 doctorants de l'INP à la FENS 2024Sofia (doctorante équipe 7), Charbel (doctorant équipes 3 et 9) et Jehanne (doctorante équipe 5) ont participé et présenté des posters à FENS 2024 à Vienne (Autriche). Ce fut une expérience enrichissante de discuter de leurs travaux avec leurs pairs, d'assister à des présentations sur des recherches novatrices dans nos domaines respectifs, et de déguster des plats typiques autrichiens avec d'autres membres de NeuroMarseille et d’ailleurs.
-
New master student in team 1Rafael Godoy, recipient of the prestigious Eiffel Excellence Scholarship, recently started a two-month internship in the Neural Plasticity and Degeneration team. Originally from João Pessoa, Brazil, he is currently pursuing a Master's degree in Neurosciences at the Aix-Marseille University.
During his internship, he will be working on the effects of MT5-MMP on neuroinflammation and intracellular trafficking.
-
l'INP à l'honneur dans la ProvenceDans son édition du vendredi 31 mai 2024, La Provence mettait l'INP à l'honneur dans son dossier sur la maladie d'Alzheimer. Le Pr Mathieu Ceccaldi (Service de Neurologie et Neuropsychologie Adultes & équipe 9) était interrogé sur les nouveaux traitements, pendant que François Devred (équipe 9) et Santiago Rivera (équipe 1) étaient eux interrogés sur les travaux des "six équipes qui bossent à temps plein dans ce "gros" laboratoire français de recherche sur Alzheimer"
-
New trainee - Team 4Carla Djian joined our team for her 1-month M1 internship. Carla is a neuroscience master student at AMU.
Welcome!
-
APP at the INPThe last 2 weeks, several INP teams hosted M1 students for their APP (Apprentissage Par Projet). For many, it was a first experience in a research lab! Each APP is organized around a larger project (Alzheimer's Disease, Myelin, Functional imaging) and students rotate between different labs of NeuroMarseille.
Thanks to Laurence, Christine (Team 1), Theresa, Fanny (Team 7), Naz and Marine (Team 4) for mentoring all these students!
-
MEDIM 2024 - retour d'expérienceDu lundi 15 au vendredi 19 avril 2024 s'est tenue, toujours avec succès, la troisième édition de la formation MedIM (Méthodes d'étude des Interactions Moléculaires) co-organisée par la Plateforme INteractome Timone (PINT) de l’INP, la plateforme de Biologie Structurale de l’AFMB et les plateformes de l’IMM, toutes trois labellisées "Plateformes Technologiques Aix-Marseille".
Pages
L'INP en chiffres
- 126 membres
- 44 chercheurs
- 48 chercheurs assistants
- 12 post-doctorants
- 11 doctorants
Pedro thesis rehearsal
Chiara received a prize for the best master’s thesis
Congratulations to Chiara Bordier (team 2 SynapTau) for receiving the GBM (Association for Biochemistry and Molecular Biology) Master Prize for the best master’s thesis! This year, Professor Lichtenthaler from Technische Universität München and the DZNE presented this honour, marking the fourth time it has been awarded. Chiara's award-winning research explored the impact of Tau protein on nuclear organization and chromatin dynamics in neurodegenerative diseases, highlighting its crucial role in nuclear tension and stress response.
INP & VH invited to the "Imagining the futur of cancer treatments" symposium
INP and Vect-Horus both participated to the symposium “Imagining the future of cancer treatments” (~100 participants) organized by the Translate-It departement of CRCM in Luminy.
3 doctorants de l'INP à la FENS 2024
Sofia (doctorante équipe 7), Charbel (doctorant équipes 3 et 9) et Jehanne (doctorante équipe 5) ont participé et présenté des posters à FENS 2024 à Vienne (Autriche). Ce fut une expérience enrichissante de discuter de leurs travaux avec leurs pairs, d'assister à des présentations sur des recherches novatrices dans nos domaines respectifs, et de déguster des plats typiques autrichiens avec d'autres membres de NeuroMarseille et d’ailleurs.
New master student in team 1
Rafael Godoy, recipient of the prestigious Eiffel Excellence Scholarship, recently started a two-month internship in the Neural Plasticity and Degeneration team. Originally from João Pessoa, Brazil, he is currently pursuing a Master's degree in Neurosciences at the Aix-Marseille University.
During his internship, he will be working on the effects of MT5-MMP on neuroinflammation and intracellular trafficking.
l'INP à l'honneur dans la Provence
Dans son édition du vendredi 31 mai 2024, La Provence mettait l'INP à l'honneur dans son dossier sur la maladie d'Alzheimer. Le Pr Mathieu Ceccaldi (Service de Neurologie et Neuropsychologie Adultes & équipe 9) était interrogé sur les nouveaux traitements, pendant que François Devred (équipe 9) et Santiago Rivera (équipe 1) étaient eux interrogés sur les travaux des "six équipes qui bossent à temps plein dans ce "gros" laboratoire français de recherche sur Alzheimer"
New trainee - Team 4
Carla Djian joined our team for her 1-month M1 internship. Carla is a neuroscience master student at AMU.
Welcome!
APP at the INP
The last 2 weeks, several INP teams hosted M1 students for their APP (Apprentissage Par Projet). For many, it was a first experience in a research lab! Each APP is organized around a larger project (Alzheimer's Disease, Myelin, Functional imaging) and students rotate between different labs of NeuroMarseille.
Thanks to Laurence, Christine (Team 1), Theresa, Fanny (Team 7), Naz and Marine (Team 4) for mentoring all these students!
Agenda
Pedro thesis rehearsal
Pedro Belio Mairal thesis defense rehearsal
Abstract :
Alzheimer’s disease (AD) is a neurodegenerative disorder with two major hallmarks: 1)amyloid B (AB) plaques in the brain parenchyma, and 2) neurofibrillary tangles. The recent FDA approval of 3 anti-AB monoclonal antibodies has downplayed some of the existent doubts on the Amyloid hypothesis, but the efficacy of these treatments is limited.
In this context, the precursor of A, C99, is gaining momentum as a neurotoxic factor on its own, and new secretases of the amyloid precursor protein (APP) have been identified. Together, these elements provide new avenues for the study of novel pathological mechanisms and anti-amyloid strategies in AD. Membrane-type 5 matrix metalloproteinase (MT5-MMP) is a recently described APP secretase, cleaving at the n-site. Knockout of MT5-MMP prevented amyloidogenesis and
neuroinflammation in an AD mouse model, and deletion of MT5-MMP transmembrane (TM) and/or intracellular (IC) domains decreased C99 and A levels in human cells. In this thesis, I explored the consequences of MT5-MMP depletion in human neurons and astrocytes and the potential of MT5-MMP TM and IC to modulate C99 and AB levels in an in vitro AD model. In my thesis, I describe an important role of MT5-MMP in dendritic arborization and glial physiology in human neurons and astrocytes. Moreover, I revealed the different roles of MT5-MMP TM and IC in C99 and AB accumulation. Modifications of the MT5-MMP IC changed C99 trafficking, with divergent consequences on C99 and AB levels. Finally, synthetic peptides mimicking certain MT5-MMP IC variants demonstrate the utility of MT5-MMP-based strategies to tackle C99 accumulation.
My PhD thesis expands our knowledge of the roles of specific MT5-MMP domains. Moreover, it provides a framework to exploit the potential of MT5-MMP unique properties for modulating C99 and confirms MT5-MMP as a valuable therapeutic target for preventing amyloidogenesis in AD.
Team 1: Guest seminar: Dr. Nicolas Sergeant
Nicolas SERGEANT is an Inserm Research Director who, from the natural history of Alzheimer’s disease (AD), the development of cell drug-screening models against AD and Tauopathies, and also thanks to a long-term collaboration with the organic chemistry laboratory of Pr. Patricia Melnyk has co-developed small anti-Alzheimer’s drugs that mitigate the pathophysiology of Alzheimer’s disease. One of these is currently in clinical phase II by a PharmD Company. He is also delighted to identify and validate biomarkers to assess neurodegenerative processes in neurological disorders and develop gene therapy using a molecular decoy strategy.
Seminar title: Bio-orthogonal chemistry as a tool for biological target identification and deciphering the mechanism of action of small anti-Alzheimer drug candidates
Abstract:
Our research has the potential to significantly impact the development of Alzheimer’s disease (AD) modifying drugs. Targeting amyloid deposition and neurofibrillary degeneration, along with neuroinflammation, is a challenging pharmacological strategy. We have synthesized five families of drugs, originally derived from chloroquine or amodiaquine and computer-assisted pharmacophore design, to achieve this goal (Sergeant et al., 2019; Tautou et al., 2021). Among these, novel polyaminobiaryl compounds, including PEL24-199, were produced and shown to repress amyloid production in vitro. In vivo, this water-soluble drug led to the recovery of short and long-term memory in transgenic animal models of both pathological processes of AD. This recovery was associated with a reduced Tau and amyloid pathology and the reduction of astrogliosis and neuroinflammation in both models. The drugs’ target is unknown, and based on the pharmacophore chemical structure, bioorthogonal chemistry was used to covalently couple the drug to the biological target and click-chemistry to isolate, purify, and identify the target of our drugs. This strategy thus enables, based on a phenotyping hit-screening, the identification of potent novel drug-directed development of anti-Alzheimer disease strategies, offering hope for the future of AD treatment.
INP external seminar : Anissa Jhumka
more info to come
David BLUM Caffeine and adenosine receptors control multicellular processes leading to memory deficits in Alzheimer’s Disease
Caffeine and adenosine receptors control multicellular processes leading to memory deficits in Alzheimer’s Disease
Epidemiological and experimental studies including ours support the beneficial effect of habitual caffeine consumption in Alzheimer's Disease (AD). The underlying mechanisms remain however ill-defined but are thought to depend on its ability to block adenosine A2A receptors, found upregulated in hippocampal neurons and astrocytes of AD patients. The present seminar will highlight recent data from our group that demonstrate the ability of caffeine to control neuro-glial mechanisms linked to hippocampal memory. Moreover, the multicellular consequences of adenosine receptor upsurge found in the AD brain and unveiled using the combination of transgenic, 3D morphological and transcriptomic approaches, will be discussed together with the subsequent translational developments.
Partenaires
Aix Marseille Université | All rights reserved - Legal notice