Investigation of PB1-F2 Protein-Derived Peptide Effects on Clinical Symptoms and Inflammatory Factors in an Animal Model of Multiple Sclerosis.

Abstract

Multiple sclerosis (MS) is an autoimmune condition affecting the central nervous system (CNS), resulting in immune-mediated demyelination and neurodegeneration. The NF-κB signaling pathway is pivotal in the inflammatory processes that drive MS pathogenesis. Recent research has underscored the therapeutic potential of peptides owing to their low immunogenicity, high specificity, and minimal side effects. PB1-F2, a protein from the influenza virus, has shown the capacity to modulate inflammation by inhibiting the NF-κB pathway. Synthetic peptides were designed on the basis of the C-terminal region of PB1-F2 and evaluated for their ability to suppress NF-κB-mediated inflammatory responses. Among these peptides, RZV8 emerged as the most potent peptide and was selected for further investigation. This study aimed to explore the therapeutic effects of the intraperitoneal administration of RZV8 in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Following EAE induction in female C57BL/6J mice, the animals were treated with RZV8. Various serum inflammatory mediators, motor functions, myelination, and inflammatory cell infiltration levels were then assessed. Our results demonstrated that RZV8 administration alleviated EAE clinical severity, reducing inflammation, demyelination, and gliosis in EAE mice. We propose that the therapeutic effects of RZV8 are primarily due to its neuroprotective and anti-inflammatory properties. These results could offer new perspectives for treating neuroinflammatory diseases, such as MS, highlighting RZV8 as a potential therapeutic candidate.