Interleukin 1 Receptor and Alzheimer’s Disease-Related Neuroinflammation

Abstract

Neuroinlammation as one of the pathogenic mechanisms concerning to the development of Alzheimer's disease (AD) has aroused more atention since last decades. Amyloid beta (Aβ) peptide generation is supposed to be the initial event in AD progress, followed by neuronal impairment, neuroinlammation, and severe substantial neuronal dysfunction. Interleukin-1 receptor (IL-1R) as one of the most prevalent inlammatory mediated surface receptors, participates not only in peripheral inlammation but also in AD-related neuroinlammation. In microglia, IL-1R activation triggers the downstream signaling and the production of proinlammatory cytokines and chemokines. IL-1R signaling also participates in AD-related Aβ-induced inlammasome activation. Besides, IL-1R activation in neurons may increase APP non-amyloid pathway by modulation of APP α-secretase activity, which may prevent neurotoxic Aβ generation. Thus, the exact role of IL-1R signaling in AD development and neuronal functions is somehow tricky.

Cause or consequence? The role of IL-1 family cytokines and receptors in neuroinflammatory and neurodegenerative diseases

“…The functions of these mediators in brain homeostasis and pathology can be pleiotropic, redundant, synergic and cross-regulating, aiming to switch off or amplify the inflammatory response in a context-dependent manner. In this scenario, the IL-1R signaling could lead to the production of inflammatory cytokines and participate in Aβ-induced inflammasome activation in microglia, while it might even increase the Amyloid Precursor Protein non-amyloidogenic processing in neurons, thereby preventing neurotoxic Aβ generation ( 72 ). Overall, whether and when the different molecules belonging to the IL-1/IL-1R family are either beneficial or detrimental to neuronal function in the course of AD, and how their negative feedback mechanisms influence this, is still a matter of intense research ( 39 ).…”