Several studies have revealed a correlation between chronic inflammation and nicotinamide adenine dinucleotide (NAD⁺) metabolism, but the precise mechanism involved is unknown. Here, we report that the genetic and pharmacological inhibition of nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in the salvage pathway of NAD⁺ biosynthesis, reduced oxidative stress, inflammation, and keratinocyte DNA damage, hyperproliferation, and cell death in zebrafish models of chronic skin inflammation, while all these effects were reversed by NAD⁺ supplementation. Similarly, genetic and pharmacological inhibition of poly(ADP-ribose) (PAR) polymerase 1 (Parp1), overexpression of PAR glycohydrolase, inhibition of apoptosis-inducing factor 1, inhibition of NADPH oxidases, and reactive oxygen species (ROS) scavenging all phenocopied the effects of Nampt inhibition. Pharmacological inhibition of NADPH oxidases/NAMPT/PARP/AIFM1 axis decreased the expression of pathology-associated genes in human organotypic 3D skin models of psoriasis. Consistently, an aberrant induction of NAMPT and PARP activity, together with AIFM1 nuclear translocation, was observed in lesional skin from psoriasis patients. In conclusion, hyperactivation of PARP1 in response to ROS-induced DNA damage, fueled by NAMPT-derived NAD⁺, mediates skin inflammation through parthanatos cell death.

Inflammation is a biological response of the immune system to harmful stimuli. Importantly, inflammation is also a hallmark of several human diseases such as cancer or diabetes. Novel drugs to treat this response are constantly researched, but the formulation is usually forgotten. Cyclodextrins (CDs) are a well-known excipient for complexing and drug delivery. Anti-inflammatory drugs and bioactive compounds with similar activities have been favored from these CD processes. CDs also illustrate anti-inflammatory activity per se. This review tried to describe the capacities of CDs in this field, and is divided into two parts: Firstly, a short description of the inflammation disease (causes, symptoms, treatment) is explained; secondly, the effects of different CDs alone or forming inclusion complexes with drugs or bioactive compounds are discussed.

Psoriasis is a human chronic, immune disease with severe cutaneous and systemic manifestations. Its prevalence, among the world population, highly varies with ethnicity and geography, but not sex from remarkable low levels in Asia to 2.3% in Spain, or an impressive 11.5% in Norway. The pathogenesis of psoriasis derives from complex genetic and environmental interactions, which creates aberrant crosstalk between keratinocytes and variated immune cell, resulting in open amplified inflammatory and pro-proliferative circuits. Both, innate and adaptive immune systems are known to be involved in the response at the cellular and humoral levels. Nevertheless, the exact molecular mechanisms are still under debate. Therefore, discovering useful therapeutic targets to stretch the molecular gaps in psoriasis pathogenesis and its associated comorbidities is still mandatory. So far, some mutagenic or pharmacological studies in vitro or using comparative vertebrate models have provided critical molecular insights and directed the human research. Although highly feasible in rodents, the versatile physiology, genetic similarity to humans and outstanding molecular toolbox available, suggest that elaborate forward genetic screenings are far easier to be conducted using the zebrafish model. Thus, in this review, we intend to briefly overview psoriasis and revise in a digested fashion the preclinical research models available, emphasizing the zebrafish as a powerful tool in the study of immune effectors on the same, and how it supports the discovering of new therapies that may help in controlling this widespread disease around the globe.