Abstract
The innate immune system (IIS) represents the first line of defense against exogenous and endogenous harmful stimuli. Different types of pathogens and diverse molecules can activate the IIS via a ligand–receptor mechanism. Cytokine release, recruitment of immunocompetent cells, and inflammation constitute the initial steps in an IIS-mediated response. While balanced IIS activity can resolve a harmful event, an altered response, such as deficient or persistent IIS activity, will have a critical effect on organism homeostasis. In this regard, chronic IIS activation has been associated with a wide range of diseases, including chronic inflammatory disorders (inflammatory bowel disease, arthritis, chronic obstructive pulmonary disease, among others), cancer and, more recently, neurodegenerative disorders. The relevance of the immune response, particularly inflammation, in the context of neurodegeneration has motivated rigorous research focused on unveiling the mechanisms underlying this response. Knowledge regarding the molecular hallmarks of the innate immune response and understanding signaling pathway cross talk are critical for developing new therapeutic strategies aimed at modulating the neuroinflammatory response within the brain. In the present review, we discuss the IIS in the central nervous system, particularly the cross talk between the toll-like receptor-signaling cascade and the wingless-related MMTV integration site (Wnt) signaling pathway and its relevance in neurodegenerative disorders such as Alzheimer’s disease.
Highlights
The innate immune system (IIS) represents the first line of defense against exogenous and endogenous harmful stimuli
This controlled isolation, which is mainly established by the blood–brain barrier (BBB), initially led to the idea that the CENTRAL NERVOUS SYSTEM (CNS) was deprived of immune cells, its ability to respond to systemic and localized pathological conditions have demonstrated its capacity to exhibit an immune response but has allowed the identification of specific cells that are responsible for this function [4]
It has been recognized that the brain parenchyma constitutes an anti-inflammatory environment that is rich in anti-inflammatory mediators, such as transforming growth factor β (TGFβ) and interleukin (IL)-10, which prevent peripheral immune cell proliferation [13,14,15], providing further support to the hypothesis that glial cells within the brain are responsible for the IIS response
Summary
Received: 29 November 2016 Accepted: 09 February 2017 Published: 24 February 2017. Citation: Zolezzi JM and Inestrosa NC (2017) Wnt/TLR Dialog in Neuroinflammation, Relevance in Alzheimer’s Disease. We discuss the IIS in the central nervous system, the cross talk between the toll-like receptor-signaling cascade and the wingless-related MMTV integration site (Wnt) signaling pathway and its relevance in neurodegenerative disorders such as Alzheimer’s disease. The CNS constitutes a highly specialized structure with neuronal physiology depending on the fulfillment of specific microenvironmental requirements, which are necessary to control the molecular and cellular efflux/influx between the CNS and blood [1,2,3] This controlled isolation, which is mainly established by the blood–brain barrier (BBB), initially led to the idea that the CNS was deprived of immune cells, its ability to respond to systemic and localized pathological conditions have demonstrated its capacity to exhibit an immune response but has allowed the identification of specific cells that are responsible for this function [4]. We summarize some of the relevant scientific evidence suggesting that the cross talk between TLR and Wnt signaling plays a relevant role in neurodegenerative disorders, in AD
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