HNK-1 Carrier Glycoproteins Are Decreased in the Alzheimer's Disease Brain
Por:
García-Ayllón MS, Botella-López A, Cuchillo-Ibañez I, Rábano A, Andreasen N, Blennow K, Ávila J and Saez J
Publicada:
1 ene 2017
Resumen:
The human natural killer-1 (HNK-1), 3-sulfonated glucuronic acid, is a glycoepitope marker of cell adhesion that participates in cell-cell and cell-extracellular matrix interactions and in neurite growth. Very little is known about the regulation of the HNK-1 glycan in neurodegenerative disease, particularly in Alzheimer's disease (AD). In this study, we investigate changes in the levels of HNK-1 carrier glycoproteins in AD. We demonstrate an overall decrease in HNK-1 immunoreactivity in glycoproteins extracted from the frontal cortex of AD subjects, compared with levels from non-demented controls (NDC). Immunoblotting of ventricular post-mortem and lumbar ante-mortem cerebrospinal fluid with HNK-1 antibodies indicate similar levels of carrier glycoproteins in AD and NDC samples. Decrease in HNK-1 carrier glycoproteins were not paralleled by changes in messenger RNA (mRNA) levels of the enzymes involved in the synthesis of the glycoepitope, beta-1,4-galactosyltransferase (beta 4GalT), glucuronyltransferases GlcAT-P and GlcAT-S, or sulfotransferase HNK-1ST. Over-expression of amyloid precursor protein in Tg2576 transgenic mice and in vitro treatment of SH-SY5Y neuroblastoma cells with the amyloidogenic A beta 42 peptide resulted in a decrease in HNK-1 immunoreactivity levels in brain and cellular extracts, whereas the levels of soluble HNK-1 glycoproteins detected in culture media were not affected by A beta treatment. HNK-1 levels remain unaffected in the brain extracts of Tg-VLW mice, a model of mutant hyperphosphorylated tau, and in SH-SY5Y cells over-expressing hyperphosphorylated wild-type tau. These results provide evidence that cellular levels of HNK-1 carrier glycoforms are decreased in the brain of AD subjects, probably influenced by the beta-amyloid protein.
Filiaciones:
:
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Sant Joan d'Alacant, Spain.
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Sant Joan d'Alacant, Spain.
Unidad de Investigación, Hospital General Universitario de Elche, FISABIO, Elche, Spain.
:
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Sant Joan d'Alacant, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Sant Joan d'Alacant, Spain
:
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Sant Joan d'Alacant, Spain
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Sant Joan d'Alacant, Spain
Rábano A:
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Sant Joan d'Alacant, Spain
Banco de Tejidos de la Fundación CIEN, CIEN Foundation, Carlos III Institute of Health, Alzheimer Center Reina Sofia Foundation, Madrid, Spain
Andreasen N:
Karolinska Institute-Alzheimer Disease Research center, Stockholm, Sweden
Blennow K:
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden
Ávila J:
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Sant Joan d'Alacant, Spain
Centro de Biología Molecular "Severo Ochoa", Universidad, Autónoma de Madrid, Consejo Superior de Investigaciones Científicas, Cantoblanco, Madrid, Spain
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