Projektbeschreibung
Einblick in den Lebenszyklus von Myelin
Neuronale Axone bzw. Nervenbahnen sind von isolierenden Myelinscheiden umhüllt, die für eine schnellere und effizientere Reizweiterleitung sorgen. Dieses Myelin wird in der Entwicklungsphase erzeugt, im Erwachsenenalter nur noch begrenzt neu gebildet und im Alter zunehmend abgebaut. Das EU-finanzierte Projekt NETWORK untersucht die Interaktion zwischen myelinproduzierenden Oligodendrozyten und anderen Gliazellen in verschiedenen Stadien des Myelin-Lebenszyklus. Erkenntnisse darüber, wie Gliazellen ihren Stoffwechsel verändern, wenn Myelin abgebaut wird, könnten die Forschung zu altersbedingten und neurodegenerativen Krankheiten wie Alzheimer-Demenz wesentlich vorantreiben.
Ziel
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.
Wissenschaftliches Gebiet
Schlüsselbegriffe
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-ADG - Advanced GrantGastgebende Einrichtung
80333 Muenchen
Deutschland