Decreased generation of C-terminal fragments of ApoER2 and increased reelin expression in Alzheimer's disease
Por:
Mata-Balaguer T, Cuchillo-Ibañez I, Calero M, Ferrer I and Saez J
Publicada:
1 jul 2018
Resumen:
Increasing evidence indicates that altered reelin signaling could contribute to synaptic dysfunction in Alzheimer's disease (AD). We found that reelin protein and mRNA levels were increased in the AD brain (particularly at advanced Braak stages in apolipoprotein E4 noncarriers), compared with that of control subjects. The beta-amyloid (A) protein impairs reelin activity and increases reelin expression through a mechanism that is not yet understood. To explore that mechanism, we examined the effect of A beta aa 1-42 (A beta(42)) on DNA methylation of the RELN promoter and the processing of reelin receptor apolipoprotein E receptor 2 (ApoER2) in differentiated SH-SY5Y cells because ApoER2 C-terminal fragments (CTFs), generated after reelin binding, regulate reelin expression. We found that A beta(42) decreased nuclear levels of DNA-methyltransferase 1. However, RELN promoter methylation did not change in A beta(42)-treated cells or in AD brain extracts. Instead, the levels of ApoER2-CTF appeared significantly lower in A beta(42)-treated cells and in AD extracts from advanced Braak stages of apolipoprotein E4 noncarriers. Our data show that ApoER2-CTF levels are decreased, whereas reelin expression is increased in AD brain at advanced Braak stages and after A treatment, supporting the view that ApoER2-CTF exerts a modulatory role on reelin expression. -Mata-Balaguer, T., Cuchillo-Ibanez, I., Calero, M., Ferrer, I., Saez-Valero, J. Decreased generation of C-terminal fragments of ApoER2 and increased reelin expression in Alzheimer's disease.
Filiaciones:
Mata-Balaguer T:
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-Consejo Superior de Investigaciones Cientificas (CSIC), Sant Joan d'Alacant, Alicante, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
:
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-Consejo Superior de Investigaciones Cientificas (CSIC), Sant Joan d'Alacant, Alicante, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Calero M:
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Alzheimer Disease Research Unit, Centro Nacional de Investigación en Enfermedades Neurológicas (CIEN) Foundation, Queen Sofia Foundation Alzheimer Center, Madrid, Spain
Chronic Disease Programme, Carlos III Institute of Health, Madrid, Spain
Ferrer I:
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Instituto de Neuropatología, Hospital Universitario de Bellvitge, Universidad de Barcelona, Hospitalet de Llobregat, Barcelona, Spain
Saez J:
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-Consejo Superior de Investigaciones Cientificas (CSIC), Sant Joan d'Alacant, Alicante, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
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