Title:β-Amyloid is an Immunopeptide and Alzheimer’s is an Autoimmune Disease
Volume: 18
Issue: 11
关键词:
阿尔茨海默病、痴呆、神经炎症、自身免疫、细胞因子、抗菌肽、β-淀粉样蛋白、免疫肽。
摘要:
Background: As new biomolecular targets for Alzheimer’s disease (AD) emerge, there
is a tendency to regard these as mutually exclusive and in competition, culminating in declarations
that since the “amyloid hypothesis is dead” it needs to be replaced by completely different theories.
However, given the well-described role of misfolding peptides, particularly β-amyloid (Aβ), in the
pathogenesis of AD, the need for a broad-based conceptualization of AD, coalescing different theories
into a single harmonized explanation emerges as a viable alternative. Incorporating protein aggregation
mechanisms of AD into a more widely-encompassing immunopathic model of AD could
accomplish such a goal-a goal which could be achieved by repositioning the role of Aβ as an immunopeptide.
Conclusion: This review presents the concept that Aβ is an immunopeptide and that AD is an autoimmune
disease in which Aβ is a key molecular player. Being a peptide with the capacity to alter
immune function, Aβ is an immunopeptide; having both antimicrobial and immunomodulatory activities,
Aβ is a host defense peptide; having most of the defining properties of cytokines, Aβ satisfies
the broad definition of cytokine-the prototypic immunopeptide subtype. In addition to these immunoactivities,
Aβ is also directly and independently cytotoxic to neurons by both necrotic and
apoptotic mechanisms. Therefore, following brain exposure to immune-instigating stimuli, the innate
immune system is activated, leading to the release of Aβ as an immunopeptide (functioning as
a host defense peptide or cytokine), which subsequently inflicts a misdirected attack upon the host
neurons-an autoimmune event.