Biomaterial Database

Targeting Cell Death Pathways for Therapeutic Intervention in Kidney Diseases. 2016

Jay P Garg, and Domagoj Vucic

Product Development, Departments of Immunology, Infectious Diseases, and Ophthalmology, Genentech, South San Francisco, CA.

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.

UI	MeSH Term	Description	Entries
D007674	Kidney Diseases	Pathological processes of the KIDNEY or its component tissues.	Disease, Kidney,Diseases, Kidney,Kidney Disease
D009336	Necrosis	The death of cells in an organ or tissue due to disease, injury or failure of the blood supply.
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015398	Signal Transduction	The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.	Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015427	Reperfusion Injury	Adverse functional, metabolic, or structural changes in tissues that result from the restoration of blood flow to the tissue (REPERFUSION) following ISCHEMIA.	Ischemia-Reperfusion Injury,Injury, Ischemia-Reperfusion,Injury, Reperfusion,Reperfusion Damage,Damage, Reperfusion,Injury, Ischemia Reperfusion,Ischemia Reperfusion Injury,Ischemia-Reperfusion Injuries,Reperfusion Damages,Reperfusion Injuries
D016923	Cell Death	The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.	Death, Cell
D017209	Apoptosis	A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.	Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D053422	Receptor-Interacting Protein Serine-Threonine Kinases	A family of serine-threonine kinases that plays a role in intracellular signal transduction by interacting with a variety of signaling adaptor proteins such as CRADD SIGNALING ADAPTOR PROTEIN; TNF RECEPTOR-ASSOCIATED FACTOR 2; and TNF RECEPTOR-ASSOCIATED DEATH DOMAIN PROTEIN. Although they were initially described as death domain-binding adaptor proteins, members of this family may contain other protein-binding domains such as those involving caspase activation and recruitment.	RIP Serine-Threonine Kinases,RIP (Receptor Interacting Protein),RIP Serine-Threonine Kinase,Receptor Interacting Protein RIP,Receptor-Interacting Protein Serine-Threonine Kinase 1,Receptor-Interacting Protein Serine-Threonine Kinase 3,Kinase, RIP Serine-Threonine,Kinases, RIP Serine-Threonine,RIP Serine Threonine Kinase,RIP Serine Threonine Kinases,Receptor Interacting Protein Serine Threonine Kinase 1,Receptor Interacting Protein Serine Threonine Kinase 3,Receptor Interacting Protein Serine Threonine Kinases,Serine-Threonine Kinase, RIP,Serine-Threonine Kinases, RIP
D058186	Acute Kidney Injury	Abrupt reduction in kidney function. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.	Acute Kidney Failure,Acute Kidney Insufficiency,Acute Renal Failure,Acute Renal Injury,Acute Renal Insufficiency,Kidney Failure, Acute,Kidney Insufficiency, Acute,Renal Failure, Acute,Renal Insufficiency, Acute,Acute Kidney Failures,Acute Kidney Injuries,Acute Kidney Insufficiencies,Acute Renal Failures,Acute Renal Injuries,Acute Renal Insufficiencies,Kidney Failures, Acute,Kidney Injuries, Acute,Kidney Injury, Acute,Kidney Insufficiencies, Acute,Renal Failures, Acute,Renal Injuries, Acute,Renal Injury, Acute,Renal Insufficiencies, Acute
D058990	Molecular Targeted Therapy	Treatments with drugs which interact with or block synthesis of specific cellular components characteristic of the individual's disease in order to stop or interrupt the specific biochemical dysfunction involved in progression of the disease.	Targeted Molecular Therapy,Molecular Targeted Therapies,Molecular Therapy, Targeted,Targeted Molecular Therapies,Targeted Therapy, Molecular,Therapy, Molecular Targeted,Therapy, Targeted Molecular