Affiliation:
1. Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling Hospital of Stomatology, Jilin University Changchun China
2. Department of Orthodontics Hospital of Stomatology, Jilin University Changchun China
3. Key Laboratory of Molecular Epigenetics, Ministry of Education Institute of Genetics and Cytology, Northeast Normal University Changchun China
Abstract
AbstractExtracellular elastin‐derived peptides (EDPs) accumulate in the aging brain and have been associated with vascular dementia and Alzheimer's disease (AD). The activation of inflammatory processes in glial cells with EDP treatment has received attention, but not in neurons. To properly understand EDPs' pathogenic significance, the impact on neuronal function and neuron–microglia crosstalk was explored further. Among the EDP molecules, Val‐Gly‐Val‐Ala‐Pro‐Gly (VGVAPG) is a typical repeating hexapeptide. Here, we observed that EDPs‐VGVAPG influenced neuronal survival and morphology in a dose‐dependent manner. High concentrations of VGVAPG induced synapse loss and microglia hyperactivation in vivo and in vitro. Following EDP incubation, galectin 3 (Gal‐3) released by neurons served as a chemokine, attracting microglial engulfment. Blocking Gal‐3 and EDP binding remedied synapse loss in neurons and phagocytosis in microglia. In response to the accumulation of EDPs, proteomics in matrix remodeling and cytoskeleton dynamics, such as a disintegrin and metalloproteinase (ADAM) family, were engaged. These findings in extracellular EDPs provided more evidence for the relationship between aging and neuron dysfunction, increasing the insight of neuroinflammatory responses and the development of new specialized extracellular matrix remolding‐targeted therapy options for dementia or other neurodegenerative disease.
Funder
Natural Science Foundation of Jilin Province
Subject
Cellular and Molecular Neuroscience,Biochemistry