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A? oligomers promote oligodendrocyte differentiation and maturation via integrin ?1 and Fyn kinase signaling.

ABSTRACT: Alzheimer´s disease (AD) is characterized by a progressive cognitive decline that correlates with the levels of amyloid ?-peptide (A?) oligomers. Strong evidences connect changes of oligodendrocyte function with the onset of neurodegeneration in AD. However, the mechanisms controlling oligodendrocyte responses to A? are still elusive. Here, we tested the role of A? in oligodendrocyte differentiation, maturation, and survival in isolated oligodendrocytes and in organotypic cerebellar slices. We found that A? peptides specifically induced local translation of 18.5-kDa myelin basic protein (MBP) isoform in distal cell processes concomitant with an increase of process complexity of MBP-expressing oligodendrocytes. A? oligomers required integrin ?1 receptor, Src-family kinase Fyn and Ca²⁺/CaMKII as effectors to modulate MBP protein expression. The pharmacological inhibition of Fyn kinase also attenuated oligodendrocyte differentiation and survival induced by A? oligomers. Similarly, using ex vivo organotypic cerebellar slices A? promoted MBP upregulation through Fyn kinase, and modulated oligodendrocyte population dynamics by inducing cell proliferation and differentiation. Importantly, application of A? to cerebellar organotypic slices enhanced remyelination and oligodendrocyte lineage recovery in lysolecithin (LPC)-induced demyelination. These data reveal an important role of A? in oligodendrocyte lineage function and maturation, which may be relevant to AD pathogenesis.

SUBMITTER: Quintela-Lopez T

PROVIDER: S-EPMC6554322 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Aβ oligomers promote oligodendrocyte differentiation and maturation via integrin β1 and Fyn kinase signaling.

Quintela-López Tania T Ortiz-Sanz Carolina C Serrano-Regal Mari Paz MP Gaminde-Blasco Adhara A Valero Jorge J Baleriola Jimena J Sánchez-Gómez Maria Victoria MV Matute Carlos C Alberdi Elena E

Cell death & disease 20190606 6

Alzheimer´s disease (AD) is characterized by a progressive cognitive decline that correlates with the levels of amyloid β-peptide (Aβ) oligomers. Strong evidences connect changes of oligodendrocyte function with the onset of neurodegeneration in AD. However, the mechanisms controlling oligodendrocyte responses to Aβ are still elusive. Here, we tested the role of Aβ in oligodendrocyte differentiation, maturation, and survival in isolated oligodendrocytes and in organotypic cerebellar slices. We f ...[more]

PMID: 31171765

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Dataset Information

A? oligomers promote oligodendrocyte differentiation and maturation via integrin ?1 and Fyn kinase signaling.

Publications

Aβ oligomers promote oligodendrocyte differentiation and maturation via integrin β1 and Fyn kinase signaling.

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