Descrizione del progetto
Informazioni sul ciclo di vita della mielina
Gli assoni neuronali sono isolati grazie alla guaina mielinica, la quale garantisce che i segnali elettrici siano elaborati con maggiore velocità e con un’efficienza migliore. La mielina è sintetizzata durante lo sviluppo, mentre più avanti, nel corso dell’età adulta, ha un ricambio limitato e si degrada durante l’invecchiamento. L’obiettivo del progetto NETWORK, finanziato dall’UE, è capire in che modo gli oligodendrociti che producono la mielina interagiscono con altre cellule gliali nelle diverse fasi del ciclo di vita della mielina. Capire le modalità con cui il metabolismo delle cellule gliali cambia in funzione della degenerazione della mielina ha importanti conseguenze per le malattie correlate all’età e i disturbi neurodegenerativi, quali il morbo di Alzheimer.
Obiettivo
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.
Campo scientifico
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-ADG - Advanced GrantIstituzione ospitante
80333 Muenchen
Germania