Modulation of immune responses by nicotinic acetylcholine receptors (nAChRs) and their implications for neuroinflammation in Alzheimer’s Disease (AD)

Abstract

Alzheimer’s Disease (AD) is a gradual neurodegenerative disease in which several factors in addition to Aβ plaques and tau tangles contribute to the chronic neuroinflammatory state that is incidental to the pathogenesis of the disease. Over the last several years, special concern has been paid to the fact that functional activation of nicotinic acetylcholine receptors (nAChRs), especially the α-7 subtype, can exert an immune-regulatory effect. Activation of the cholinergic anti-inflammatory pathway through nAChRs present on immune cells, both microglia and macrophages have recently become a therapeutic target in neurodegenerative diseases. This dissertation seeks to better understand the immunomodulatory role of nAChRs, in AD. In this review, the impact of activation and inhibition of certain sutypes of nAChR on cytokine release, the activation of microglial cells, and the survival of neurons is discussed. Moreover, this critical essay evaluates the evidence that supports the relationship between cholinergic dysfunction and overexaggerated inflammatory responses in AD, and how the pharmacological modulation of nAChRs could serve as a new approach to reduce disease progression. The molecular pathways triggered by nAChR activation which lead to immune modulation in AD are reviewed by the synthesis of existing knowledge in molecular, cellular and preclinical studies. Knowledge of these mechanisms may shed light into future treatment strategies and a more thorough understanding of complex inter-relationships between the nervous and immune systems in neurodegenerative disease.