Immune activation in the central nervous system involves mostly microglia in response to pathogen invasion or tissue damage, which react, promoting a self-limiting inflammatory response aimed to restore homeostasis. However, prolonged, uncontrolled inflammation may result in the production by microglia of neurotoxic factors that lead to the amplification of the disease state and tissue damage. In particular, specific inducers of inflammation associated with neurodegenerative diseases activate inflammatory processes that result in the production of a number of mediators and cytokines that enhance neurodegenerative processes. Phosphoinositide 3-kinases (PI3Ks) constitute a family of enzymes regulating a wide range of activity, including signal transduction. Recent studies have focused attention on the intracellular role of PI3K and its contribution to neurodegenerative processes. This review illustrates and discusses recent findings about the role of this signaling pathway in the modulation of microglia neuroinflammatory responses linked to neurodegeneration. Finally, we discuss the modulation of PI3K as a potential therapeutic approach helpful for developing innovative therapeutic strategies in neurodegenerative diseases.

In recent years, there has been considerable research showing that coffee consumption seems to be beneficial to human health, as it contains a mixture of different bioactive compounds such as chlorogenic acids, caffeic acid, alkaloids, diterpenes and polyphenols. Neurodegenerative diseases (NDs) are debilitating, and non-curable diseases associated with impaired central, peripheral and muscle nervous systems. Several studies demonstrate that neuroinflammation mediated by glial cells—such as microglia and astrocytes—is a critical factor contributing to neurodegeneration that causes the dysfunction of brain homeostasis, resulting in a progressive loss of structure, function, and number of neuronal cells. This happens over time and leads to brain damage and physical impairment. The most known chronic NDs are represented by Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD). According to epidemiological studies, regular coffee consumption is associated with a lower risk of neurodegenerative diseases. In this review, we summarize the latest research about the potential effects of caffeine in neurodegenerative disorders prevention and discuss the role of controlled caffeine delivery systems in maintaining high plasma caffeine concentrations for an extended time.

Inflammaging is a term used to describe the tight relationship between low-grade chronic inflammation and aging that occurs during physiological aging in the absence of evident infection. This condition has been linked to a broad spectrum of age-related disorders in various organs including the brain. Inflammaging represents a highly significant risk factor for the development and progression of age-related conditions, including neurodegenerative diseases which are characterized by the progressive dysfunction and degeneration of neurons in the brain and peripheral nervous system. Curcumin is a widely studied polyphenol isolated from Curcuma longa with a variety of pharmacologic properties. It is well-known for its healing properties and has been extensively used in Asian medicine to treat a variety of illness conditions. The number of studies that suggest beneficial effects of curcumin on brain pathologies and age-related diseases is increasing. Curcumin is able to inhibit the formation of reactive-oxygen species and other pro-inflammatory mediators that are believed to play a pivotal role in many age-related diseases. Curcumin has been recently proposed as a potential useful remedy against neurodegenerative disorders and brain ageing. In light of this, our current review aims to discuss the potential positive effects of Curcumin on the possibility to control inflammaging emphasizing the possible modulation of inflammaging processes in neurodegenerative diseases.

Vitamin C (Vit C) is anutrient present in many foods, particularly citrus fruits, green vegetables, tomatoes, and potatoes. Vit C is studied for its applications in the prevention and management of different pathologies, including neurodegenerative diseases. Neuroinflammation is a defense mechanism activated by a stimulus or an insult that is aimed at the preservation of the brain by promoting tissue repair and removing cellular debris; however, persistent inflammatory responses are detrimental and may lead to the pathogenesis and progression of neurodegenerative diseases like Parkinson’s disease (PD) and Alzheimer’s disease. PD is one of the most common chronic progressive neurodegenerative disorders, and oxidative stress is one of the most important factors involved in its pathogenesis and progression.Due to this, research on antioxidant and anti-inflammatory compounds is an important target for counteracting neurodegenerative diseases, including PD. In the central nervous system, the presence of Vit C in the brain is higher than in other body districts, but why and how this occurs is still unknown. In this research, Vit C, with its anti-inflammatory and anti-oxidative properties, is studied to better understand its contribution to brain protection; in particular, we have investigated the neuroprotective effects of Vit C in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of PD and its role in the modulation of neuroinflammation. First, we observed that Vit C significantly decreased the MPTP-induced loss of tyrosine hydroxylase (TH)-positive dopaminergic neuronal cells in the substantia nigra, as well as microglial cell activation and astrogliosis. Furthermore, gait and spontaneous locomotor activity, evaluated by an automated treadmill and the Open Field test, respectively, were partially ameliorated by Vit C treatment in MPTP-intoxicated animals. In relation to neuroinflammation, results show that Vit C reduced the protein and mRNA expression of inflammatory cytokines such as IL-6, TLR4, TNF-α, iNOS, and CD40, while anti-inflammatory proteins such as IL-10, CD163, TGF-β, and IL-4 increased. Interestingly, we show for the first time that Vit C reduces neuroinflammation by modulating microglial polarization and astrocyte activation. Moreover, Vit C was able to reduce NLRP3 activation, which is linked to the pathogenesis of many inflammatory diseases, including neuroinflammatory disorders. In conclusion, our study provides evidence that Vit C may represent a new promising dietary supplement for the prevention and alleviation of the inflammatory cascade of PD, thus contributing to neuroprotection.

Inflammatory skin diseases include a series of disorders characterized by a strong activation of the innate and adaptive immune system in which proinflammatory cytokines play a fundamental role in supporting inflammation. Skin inflammation is a complex process influenced by various factors, including genetic and environmental factors, characterized by the dysfunction of both immune and non-immune cells. Psoriasis (PS) and atopic dermatitis (AD) are the most common chronic inflammatory conditions of the skin whose pathogeneses are very complex and multifactorial. Both diseases are characterized by an immunological dysfunction involving a predominance of Th1 and Th17 cells in PS and of Th2 cells in AD. Suppressor of cytokine signaling (SOCS) proteins are intracellular proteins that control inflammatory responses by regulating various signaling pathways activated by proinflammatory cytokines. SOCS signaling is involved in the regulation and progression of inflammatory responses in skin-resident and non-resident immune cells, and recent data suggest that these negative modulators are dysregulated in inflammatory skin diseases such as PS and AD. This review focuses on the current understanding about the role of SOCS proteins in modulating the activity of inflammatory mediators implicated in the pathogenesis of inflammatory skin diseases such as PS and AD.