Descripción del proyecto
Más datos sobre el ciclo vital de la mielina
Los axones neuronales están aislados mediante vainas de mielina que permiten el procesamiento de señales eléctricas a mayor velocidad y de forma más eficiente. La mielina se sintetiza durante el desarrollo, pero su renovación es limitada y, con el envejecimiento, entra en una fase de degradación. El objetivo del proyecto NETWORK, financiado con fondos europeos, es comprender cómo interactúan los oligodendrocitos productores de mielina con otras células gliales en diferentes fases del ciclo vital de la mielina. Comprender cómo cambia el metabolismo de las células gliales con la degeneración de la mielina tendría importantes implicaciones para las afecciones asociadas con la edad y las de tipo neurodegenerativo, como la enfermedad de Alzheimer.
Objetivo
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.
Ámbito científico
Palabras clave
Programa(s)
Régimen de financiación
ERC-ADG - Advanced GrantInstitución de acogida
80333 Muenchen
Alemania