An ανβ3 integrin-binding peptide ameliorates symptoms of chronic progressive experimental autoimmune encephalomyelitis by alleviating neuroinflammatory responses in mice.

MOG35-55 triggers chronic, progressive experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, and the clinical course of EAE in this model is characterized by macrophage infiltration, axonal demyelination/damage, and progressive paralysis. These stages are usually associated with inflammatory responses in the central nervous system (CNS). This study was designed to investigate the effects of C16, an ανβ3 integrin-binding peptide that targets integrins involved in the transendothelial migration of extravasating inflammatory cells. C16 was applied for only 2 weeks, but the benefits of this therapy lasted at least 8 weeks. Multiple histological and immunohistochemical staining studies, western blotting, enzyme-linked immunosorbent assays, electron microscopy, and cortical somatosensory-evoked potential (c-SEP) electrophysiological tests were employed to assess the degree of inflammation, axonal loss, white matter demyelination, neuronal apoptosis, extent of gliosis, expression of pro-inflammatory cytokines, and functional recovery of differently treated EAE model mice. The results showed that C16 treatment inhibited extensive leukocyte and macrophage accumulation and infiltration, reduced the expression of pro-inflammatory cytokines (tumor necrosis factor-α and interferon-γ), and thereby attenuated and delayed the progression of EAE. Moreover, astrogliosis, demyelination, and axonal and neuronal loss were all alleviated in C16-treated EAE animals, contributing to the improvement of function. These data suggest that the C16 peptide may act as a protective agent by reducing neuroinflammatory responses and improving the microenvironment.