Anti-inflammatory role of microglial alpha7 nAChRs and its role in neuroprotection

Nicotinic acetylcholine receptors (nAChRs) are widely distributed throughout the central nervous system, being expressed in neurons and non-neuronal cells, where they participate in a variety of physiological responses like memory, learning, locomotion, attention, among others. We will focus on the alpha 7 nAChR subtype, which has been implicated in neuroprotection, synaptic plasticity and neuronal survival, and is considered as a potential therapeutic target for several neurological diseases. Oxidative stress and neuroinflammation are currently considered as two of the most important pathological mechanisms common in neurodegenerative diseases such as Alzheimer, Parkinson or Huntington diseases. In this review, we will first analysed the distribution and expression of nAChR in mammalian brain. Then, we focused on the function of the alpha 7 nAChR subtype in neuronal and non-neuronal cells and its role in immune responses (cholinergic anti-inflammatory pathway). Finally, we will revise the anti-inflammatory pathway promoted via alpha 7 nAChR activation that is related to recruitment and activation of jalc2/STAT3 pathway, which on the one hand inhibits NF-kappa B nuclear translocation, and on the other hand, activates the master regulator of oxidative stress Nrf2/H0-1. This review provides a profound insight into the role of the a7 nAChR subtype in microglia and point out to microglial alpha 7/HO-1 pathway as an anti-inflammatory therapeutic target. (C) 2015 Elsevier Inc. All rights reserved.