Abstract
Neuroinflammation is a biological process by which the central nervous system responds to stimuli/injuries affecting its homeostasis. So far as this reactive response becomes exacerbated and uncontrolled, it can lead to neurodegeneration, compromising the cognitive and neuropsychiatric domains. Parallelly, modifications in the hypothalamic signaling of neuroprotective hormones linked also to the inflammatory responses of microglia and astrocytes can exacerbate these processes. To complicate the picture, modulations in the gut microbiota (GM) can induce changes in neuroinflammation, altering cognitive and neuropsychiatric functioning. We conducted a web-based search on PubMed. We described studies regarding the cross-talk among microglia and astrocytes in the neuroinflammation processes, along with the role played by the steroid hormones, and how this can reflect on cognitive decline/neurodegeneration, in particular on Alzheimer’s Disease (AD) and its neuropsychiatric manifestations. We propose and support the huge literature showing the potentiality of complementary/alternative therapeutic approaches (nutraceuticals) targeting the sustained inflammatory response, the dysregulation of hypothalamic system and the GM composition. NF-κB and Keap1/Nrf2 are the main molecular targets on which a list of nutraceuticals can modulate the altered processes. Since there are some limitations, we propose a new intervention natural treatment in terms of Oxygen-ozone (O2-O3) therapy that could be potentially used for AD pathology. Through a meta-analytic approach, we found a significant modulation of O3 on inflammation-NF-κB/NLRP3 inflammasome/Toll-Like Receptor 4 (TLR4)/Interleukin IL-17α signalling, reducing mRNA (p<0.00001 Odd Ratio (OR)=-5.25 95% CI:-7.04/-3.46) and protein (p<0.00001 OR=-4.85 95%CI:-6.89/-2.81) levels, as well as on Keap1/Nrf2 pathway. Through anti-inflammatory, immune, and steroid hormones modulation and anti-microbial activities, O3 at mild therapeutic concentrations potentiated with nutraceuticals and GM regulators could determine combinatorial effects impacting on cognitive and neurodegenerative domains, neuroinflammation and neuroendocrine signalling, directly or indirectly through the mediation of GM.
Highlights
Neuroinflammation is a defence mechanism aimed to protect the central nervous system (CNS) in response to a variety of insults, including infection, traumatic injury, toxic metabolites, or autoimmune events [1]
We support the wide literature on the crucial role that different nutraceuticals can play in neuroinflammation/steroid hormones alteration/ neurodegeneration, directly or indirectly through the manipulation of gut microbiota (GM), further and future clinical studies are needed in Alzheimer's Disease (AD)
Correlated with the well-known interactions with NF-κB, Keap1/Nrf2 and NFAT or AP-1 [166,167,168, 172] or steroid hormones system, GCs [174, 180], O3 and/or in combination with the other nutraceuticals described in Table 1 can potentially increase the immune system, decrease the neuroinflammation and modulate the neuroendocrine system, to improve/resolve the cognitive performance and neuropsychiatric symptoms
Summary
Neuroinflammation is a defence mechanism aimed to protect the central nervous system (CNS) in response to a variety of insults, including infection, traumatic injury, toxic metabolites, or autoimmune events [1]. These functions are strongly linked to a high level of chronic neuroinflammation, attributed to the activation of microglia cells and to the release of numerous pro-inflammatory cytokines [14].
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