title: Roles and regulation of neutral sphingomyelinase-2 in cellular and pathological processes.
abstract: Our understanding of the functions of ceramide signaling has advanced tremendously over the past decade. In this review, we focus on the roles and regulation of neutral sphingomyelinase 2 (nSMase2), an enzyme that generates the bioactive lipid ceramide through the hydrolysis of the membrane lipid sphingomyelin. A large body of work has now implicated nSMase2 in a diverse set of cellular functions, physiological processes, and disease pathologies. We discuss different aspects of this enzyme's regulation from transcriptional, post-translational, and biochemical. Furthermore, we highlight nSMase2 involvement in cellular processes including inflammatory signaling, exosome generation, cell growth, and apoptosis, which in turn play important roles in pathologies such as cancer metastasis, Alzheimer's disease, and other organ systems disorders. Lastly, we examine avenues where targeted nSMase2-inhibition may be clinically beneficial in disease scenarios.
authors.affiliation: Department of Medicine, Stony Brook, NY 11794, USA; The Stony Brook Cancer Center, Stony Brook, NY 11794, USA.
authors.forename: Achraf A
authors.initials: AA
authors.lastname: Shamseddine
authors.affiliation: Department of Medicine, Stony Brook, NY 11794, USA; The Stony Brook Cancer Center, Stony Brook, NY 11794, USA.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Airola
authors.affiliation: Department of Medicine, Stony Brook, NY 11794, USA; The Stony Brook Cancer Center, Stony Brook, NY 11794, USA. Electronic address: yusuf.hannun@sbumed.org.
authors.forename: Yusuf A
authors.initials: YA
authors.lastname: Hannun
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002518:Ceramides / Q000235:genetics / Q000378:metabolism; D055354:Exosomes / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011499:Protein Processing, Post-Translational / Q000235:genetics; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics / Q000378:metabolism*; D013109:Sphingomyelins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D002518:Ceramides; D009363:Neoplasm Proteins; D013109:Sphingomyelins; C491484:SMPD3 protein, human; D013108:Sphingomyelin Phosphodiesterase
keywords: Apoptosis; Ceramide; Exosomes; Inflammation; Sphingomyelinase