title: Targeting Cell Death Pathways for Therapeutic Intervention in Kidney Diseases.
abstract: Precise regulation of cell death and survival is essential for proper maintenance of organismal homeostasis, development, and the immune system. Deregulated cell death can lead to developmental defects, neuropathies, infections, and cancer. Kidney diseases, especially acute pathologies linked to ischemia-reperfusion injury, are among illnesses that profoundly are affected by improper regulation or execution of cell death pathways. Attempts to develop medicines for kidney diseases have been impacted by the complexity of these pathologies given the heterogeneous patient population and diverse etiologies. By analyzing cell death pathways activated in kidney diseases, we attempt to differentiate their importance for these pathologies with a goal of identifying those that have more profound impact and the best therapeutic potential. Although classic apoptosis still might be important, regulated necrosis pathways including necroptosis, ferroptosis, parthanatos, and mitochondrial permeability transition-associated cell death play a significantly role in kidney diseases, especially in acute kidney pathologies. Although targeting receptor-interacting protein 1 kinase appears to be the best therapeutic strategy, combination with inhibitors of other cell death pathways is likely to bring superior benefit and possible cure to patients suffering from kidney diseases.
authors.affiliation: Product Development, Departments of Immunology, Infectious Diseases, and Ophthalmology, Genentech, South San Francisco, CA.
authors.forename: Jay P
authors.initials: JP
authors.lastname: Garg
authors.affiliation: Early Discovery Biochemistry, Genentech, South San Francisco, CA. Electronic address: domagoj@gene.com.
authors.forename: Domagoj
authors.initials: D
authors.lastname: Vucic
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000378:metabolism; D017209:Apoptosis; D016923:Cell Death; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy; D058990:Molecular Targeted Therapy; D009336:Necrosis; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D053422:Receptor-Interacting Protein Serine-Threonine Kinases
keywords: RIP1 kinase; acute kidney injury; apoptosis; ischemia reperfusion injury; necroptosis