Description du projet
Plongée dans le cycle de vie de la myéline
Les axones des neurones sont isolés par des gaines de myéline qui assurent un traitement plus rapide et plus efficace des signaux électriques. La myéline est synthétisée au cours du développement et présente, à l’état adulte, un renouvellement limité, qui est suivi d’une phase de dégradation pendant le vieillissement. L’objectif du projet NETWORK, financé par l’UE, est de comprendre l’interaction entre les oligodendrocytes producteurs de myéline et les autres cellules gliales à différents stades du cycle de vie de la myéline. Comprendre la manière dont le métabolisme des cellules gliales change sous l’effet de la dégénérescence myélinique a des conséquences importantes pour les maladies liées à l’âge et les troubles neurodégénératifs, comme la maladie d’Alzheimer.
Objectif
Myelin is an abundant, lipid-rich membrane structure formed by oligodendrocytes, each of which extends numerous processes to form distinct myelin internode segments along axons, thereby increasing neural processing speed and energetic efficiency. Myelin undergoes a life cycle with three fundamental distinct phases of metabolism, starting with an ‘anabolic’ phase of early postnatal myelin development, followed by a homeostatic, adult state, in which turnover is low, and ending with a ‘catabolic’, myelin degradative phase in aging. Here, I hypothesize that oligodendrocytes and their myelin sheaths are metabolically connected to other glial cells, and we therefore plan to analyze how the entire glial system interacts during these distinct phases. Key is that lipoproteins may function as vehicles in this communication to connect and regulate lipid metabolism in the cells. We will use systems biology approaches to characterize how astrocytes and microglia respond to myelin assembly and disassembly. I suggest that glial cells serve as a homeostatic control system to balance and buffer changes that occur during the myelin life cycle. This system is relevant in aging, and we therefore plan to analyze how glial cells react and adapt their metabolism to age-related white matter myelin degeneration, and how lipoproteins participate in this process. We will determine the molecular anatomy of the major lipoproteins in the CNS to explore the role of lipoproteins in neurodegenerative diseases to understand both their protective functions as detoxifiers, and also their maladaptive, inflammatory functions driving pathology. We would like to propose a work program, in which we link the fundamental biology of lipid metabolism to myelin in the normal and diseased central nervous system. This approach will not only shed light on myelin biology and lipoproteins function and dysfunction, but may also open the door to new therapeutic venues for neurological disorders.
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ERC-ADG - Advanced GrantInstitution d’accueil
80333 Muenchen
Allemagne