Neuroinflammation Modulation via α7 Nicotinic Acetylcholine Receptor and Its Chaperone, RIC-3

Abstract

Nicotinic acetylcholine receptors (nAChRs) are widely expressed in or on various cell types and have diverse functions. In immune cells nAChRs regulate proliferation, differentiation and cytokine release. Specifically, activation of the α7 nAChR reduces inflammation as part of the cholinergic anti-inflammatory pathway. Here we review numerous effects of α7 nAChR activation on immune cell function and differentiation. Further, we also describe evidence implicating this receptor and its chaperone RIC-3 in diseases of the central nervous system and in neuroinflammation, focusing on multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Deregulated neuroinflammation due to dysfunction of α7 nAChR provides one explanation for involvement of this receptor and of RIC-3 in neurodegenerative diseases. In this review, we also provide evidence implicating α7 nAChRs and RIC-3 in neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) involving neuroinflammation. Besides, we will describe the therapeutic implications of activating the cholinergic anti-inflammatory pathway for diseases involving neuroinflammation.

Keywords: Alzheimer’s disease; Parkinson’s disease; RIC-3; cholinergic anti-inflammatory pathway; experimental autoimmune encephalomyelitis; multiple sclerosis; neuroinflammation; α7 nicotinic acetylcholine receptor.

Figure 1

Immunomodulation mediated by nAChRs. (A) Left pathway, the splenic vagal nerve activity via the cholinergic anti-inflammatory pathways reduces inflammation within and outside the spleen. Right pathway, the sympathetic splenic nerve via neuroadrenaline (NA) release in the spleen promotes antibody production. (B) An anti-inflammatory negative feedback loop involving monocyte expressed nAChRs.

Figure 2

Cholinergic effects of α7 nAChR on immune and glial cells.