Biomaterial Database

NAMPT and PARylation Are Involved in the Pathogenesis of Atopic Dermatitis. 2023

Ana B Arroyo, and Martín Bernal-Carrión, and Joaquín Cantón-Sandoval, and Isabel Cabas, and Raúl Corbalán-Vélez, and Teresa Martínez-Menchón, and Belén Ferri, and María L Cayuela, and Diana García-Moreno, and Victoriano Mulero

Inmunidad, Inflamación y Cáncer, Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, 30100 Murcia, Spain.

Atopic dermatitis (AD) is a chronic inflammatory skin disease of very high prevalence, especially in childhood, with no specific treatment or cure. As its pathogenesis is complex, multifactorial and not fully understood, further research is needed to increase knowledge and develop new targeted therapies. We have recently demonstrated the critical role of NAD+ and poly (ADP-ribose) (PAR) metabolism in oxidative stress and skin inflammation. Specifically, we found that hyperactivation of PARP1 in response to DNA damage induced by reactive oxygen species, and fueled by NAMPT-derived NAD+, mediated inflammation through parthanatos cell death in zebrafish and human organotypic 3D skin models of psoriasis. Furthermore, the aberrant induction of NAMPT and PARP activity was observed in the lesional skin of psoriasis patients, supporting the role of these signaling pathways in psoriasis and pointing to NAMPT and PARP1 as potential novel therapeutic targets in treating skin inflammatory disorders. In the present work, we report, for the first time, altered NAD+ and PAR metabolism in the skin of AD patients and a strong correlation between NAMPT and PARP1 expression and the lesional status of AD. Furthermore, using a human 3D organotypic skin model of AD, we demonstrate that the pharmacological inhibition of NAMPT and PARP reduces pathology-associated biomarkers. These results help to understand the complexity of AD and reveal new potential treatments for AD patients.

UI	MeSH Term	Description	Entries
D007249	Inflammation	A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.	Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D009243	NAD	A coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). (Dorland, 27th ed)	Coenzyme I,DPN,Diphosphopyridine Nucleotide,Nadide,Nicotinamide-Adenine Dinucleotide,Dihydronicotinamide Adenine Dinucleotide,NADH,Adenine Dinucleotide, Dihydronicotinamide,Dinucleotide, Dihydronicotinamide Adenine,Dinucleotide, Nicotinamide-Adenine,Nicotinamide Adenine Dinucleotide,Nucleotide, Diphosphopyridine
D011064	Poly Adenosine Diphosphate Ribose	A polynucleotide formed from the ADP-RIBOSE moiety of nicotinamide-adenine dinucleotide (NAD) by POLY(ADP-RIBOSE) POLYMERASES.	Poly ADP Ribose,Poly(ADP-Ribose),Poly-ADPR,Poly-Adenosine Diphosphate-Ribose,ADP Ribose, Poly,Diphosphate-Ribose, Poly-Adenosine,Poly ADPR,Ribose, Poly ADP
D011565	Psoriasis	A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis.	Palmoplantaris Pustulosis,Pustular Psoriasis of Palms and Soles,Pustulosis Palmaris et Plantaris,Pustulosis of Palms and Soles,Psoriases
D003876	Dermatitis, Atopic	A chronic inflammatory genetically determined disease of the skin marked by increased ability to form reagin (IgE), with increased susceptibility to allergic rhinitis and asthma, and hereditary disposition to a lowered threshold for pruritus. It is manifested by lichenification, excoriation, and crusting, mainly on the flexural surfaces of the elbow and knee. In infants it is known as infantile eczema.	Eczema, Atopic,Eczema, Infantile,Neurodermatitis, Atopic,Neurodermatitis, Disseminated,Atopic Dermatitis,Atopic Eczema,Atopic Neurodermatitis,Disseminated Neurodermatitis,Infantile Eczema
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000067856	Poly(ADP-ribose) Polymerase Inhibitors	Chemicals and drugs that inhibit the action of POLY(ADP-RIBOSE)POLYMERASES.	Inhibitors of Poly(ADP-ribose) Polymerase,PARP Inhibitor,Poly(ADP-Ribose) Polymerase Inhibitor,Poly(ADP-ribosylation) Inhibitor,Inhibitors of Poly(ADP-ribose) Polymerases,PARP Inhibitors,Poly(ADP-ribosylation) Inhibitors,Inhibitor, PARP,Inhibitors, PARP
D000071137	Poly (ADP-Ribose) Polymerase-1	A poly(ADP-ribose) polymerase that contains two ZINC FINGERS in its N-terminal DNA-binding region. It modifies NUCLEAR PROTEINS involved in chromatin architecture and BASE EXCISION REPAIR with POLY ADENOSINE DIPHOSPHATE RIBOSE.	NAD+ ADP-ribosyltransferase-1,PARP-1 Protein,PARP1 Protein,Poly (ADP-Ribose) Synthase-1,NAD+ ADP ribosyltransferase 1,PARP 1 Protein
D000074747	Poly ADP Ribosylation	Post-translational modification of proteins with POLY ADENOSINE DIPHOSPHATE RIBOSE.	PARylation,Poly(ADP-Ribosyl)ation,Poly(ADPRibosyl)ation,Poly-ADP-Ribosylation,Poly-ADPRibosylation,PolyADPRibosylation,ADP Ribosylation, Poly,ADP Ribosylations, Poly,PARylations,Poly ADP Ribosylations,Poly ADPRibosylation,Poly-ADP-Ribosylations,Poly-ADPRibosylations,PolyADPRibosylations,Ribosylation, Poly ADP,Ribosylations, Poly ADP
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia