CONCLUSIONI - Proteine correlate alla neurodegenerazione e marker di infiammazione a livello in

73 I risultati ottenuti hanno dimostrato che:

Con il progredire della malattia, a livello cerebrale si ha una riduzione dei livelli di proteina α-sin totale accompagnato da un aumento della stessa proteina a livello intestinale. Nell’invecchiamento fisiologico, i livelli di proteina tendono ad aumentare in tutti e due i tessuti presi in esame. La proteina risulta essere coinvolta nella malattia e l’analisi della sua concentrazione potrebbe costituire un buon biomarker sia a livello centrale che periferico.

I livelli dell’eterocomplesso α-sin/Aβ tendono a diminuire con il progredire della malattia sia a livello cerebrale che a livello intestinale. Nell’invecchiamento fisiologico, invece, a livello centrare si ha un aumento di eterocomplesso, mentre nel colon non si ha una significativa differenza tra i due stadi di invecchiamento. Il complesso risulta essere correlato alla malattia e potrebbe costituire un biomarker sia centrale che periferico utile alla diagnosi della malattia di Alzheimer.

L’eterocomplesso α-sin/tau nel cervello diminuisce, mentre nell’intestino non ci sono differenze significative tra i gruppi presi in esame nel nostro studio. È interessante notare come a livello cerebrale i livelli di complesso, al primo stadio della malattia, siano notevolmente più elevati rispetto al controllo, mentre nel secondo stadio si ha un cambio di andamento e risultano maggiori i livelli di α-sin/tau in topi con invecchiamento fisiologico. A livello cerebrale il complesso risulta essere coinvolto nella malattia e quindi sembra essere un biomarker centrale.

Nei topi con invecchiamento fisiologico i livelli di citochina risultano essere bassi suggerendo che non vi sia in corso un processo infiammatorio. Nei topi che presentano la malattia, i livelli di IL-1β aumentano notevolmente con l’avanzare della malattia sia nel cervello che nel colon. IL-1β è uno dei principali marker di infiammazione ed è coinvolto nella rottura della BEE tipica della malattia. L’asse intestino-cervello permette ai due organi di essere strettamente interconnessi e recenti studi hanno dimostrato che alterazioni del microbioma intestinale possono attivare citochine pro-infiammatorie e portare ad un’aumentata permeabilità della barriera intestinale con conseguente fuoriuscita di

microrganismi che entrano nel flusso sanguigno e possono attraversare la BEE. Poiché IL- 1β risulta essere coinvolta in questi processi potrebbe costituire un buon biomarker di infiammazione a livello centrale e periferico.

In conclusione, la proteina α-sin e i suoi eterocomplessi α-sin/Aβ e α-sin/tau sembrano essere coinvolti nella neurodegenerazione. Sembra sia coinvolto anche il processo infiammatorio a carico dell’intestino che, tramite l’asse intestino-cervello, può presentarsi anche a livello centrale. Questo studio, in accordo a studi in corso, apre la via a nuove prospettive future per quanto riguarda il coinvolgimento dell’infiammazione nella neurodegenerazione e l’individuazione di marker di tale processo infiammatorio.

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