Analysis of the Relationship Between Metalloprotease-9 and Tau Protein in Alzheimer's Disease
| Autor: | Javier Cázares-Apátiga, Andrés Salas-Casas, Miguel Ángel Ontiveros Torres, Charles R. Harrington, Eduardo Pérez Salazar, Ricardo Apátiga-Pérez, Pedro Cortés-Reynosa, José Luna-Muñoz, Sarita Montaño, Mario Hernandes-Alejandro, George Perry, Claude M. Wischik, Mar Pacheco-Herrero |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Tau protein tau Proteins Matrix metalloproteinase Immunofluorescence Protein Structure Secondary law.invention 03 medical and health sciences 0302 clinical medicine Western blot Confocal microscopy law Alzheimer Disease medicine Entorhinal Cortex Humans Zymography Aged Aged 80 and over Metalloproteinase medicine.diagnostic_test biology Chemistry General Neuroscience General Medicine Middle Aged Cell biology Molecular Docking Simulation Psychiatry and Mental health Clinical Psychology 030104 developmental biology Matrix Metalloproteinase 9 biology.protein Phosphorylation Female Geriatrics and Gerontology 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Journal of Alzheimer's disease : JAD. 76(2) |
| ISSN: | 1875-8908 |
| Popis: | Background Neurofibrillary tangles (NFTs) and amyloid plaques are the neuropathological hallmarks in brains with Alzheimer's disease (AD). Post-translational modifications of tau, such as phosphorylation and truncation, have been proposed as initiators in the assembly of the abnormal paired helical filaments that constitute the NFTs. Neurons and NFTs are sites of matrix metalloproteinases (MMPs). Objective The aim of this study was to analyze the relationship of MMP-9 and tau protein in brain samples with AD. Methods This study was performed on brain tissue samples from patients with early, moderate, and late AD. MMPs and tau levels were analyzed by western blot and gelatin-substrate zymography. Immunofluorescence techniques and confocal microscopy were used to analyze the presence of both proteins in NFTs. Further, molecular dynamics simulations (MDS) and protein-protein docking were conducted to predict interaction between MMP-9 and tau protein. Results MMP-9 expression was greatest in moderate and late AD, whereas MMP-2 expression was only increased in late-stage AD. Interestingly, confocal microscopy revealed NFTs in which there was co-localization of MMP-9 and tau protein. MDS and protein-protein docking predictions indicate that a high-affinity complex can be formed between MMP-9 and full-length tau protein. Conclusion These observations provide preliminary evidence of an interaction between these two proteins. Post-translational modifications of tau protein, such as C-terminal truncation or phosphorylation of amino acid residues in the MMP-9 recognition site and conformational changes in the protein, such as folding of the N-terminal sequence over the three-repeat domain, could preclude the interaction between MMP-9 and tau protein during stages of NFT development. |
| Databáze: | OpenAIRE |
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