The necroptosis pathway and its role in age-related neurodegenerative diseases: will it open up new therapeutic avenues in the next decade?
- 2 July 2020
- journal article
- review article
- Published by Informa UK Limited in Emerging Therapeutic Targets
- Vol. 24 (7), 679-693
- https://doi.org/10.1080/14728222.2020.1758668
Abstract
Introduction: Necroptosis is a programmed form of necrotic cell death. Growing evidence demonstrates that necroptosis contributes to cell demise in different pathological conditions including age-dependent neurodegenerative diseases (NDs). These findings open new avenues for understanding the mechanisms of neuronal loss in NDs, which might eventually translate into novel therapeutic interventions. Areas covered: We reviewed key aspects of necroptosis, in health and disease, focusing on evidence demonstrating its involvement in the pathogenesis of age-related NDs. We then highlight the activation of this pathway in the mechanism of axonal degeneration. We searched on PubMed the literature regarding necroptosis published between 2008 and 2020 and reviewed all publications were necroptosis was studied in the context of age-related NDs. Expert opinion: Axonal loss and neuronal death are the ultimate consequences of NDs that translate into disease phenotypes. Targeting degenerative mechanisms of the neuron appears as a strategy that might cover a wide range of diseases. Thus, the participation of necroptosis as a common mediator of neuronal demise emerges as a promising target for therapeutic intervention. Considering evidence demonstrating that necroptosis mediates axonal degeneration, we propose and discuss the potential of targeting necroptosis-mediated axonal destruction as a strategy to tackle NDs before neuronal loss occurs.Keywords
Funding Information
- funded by grants from Geroscience Center for Brain Health and Metabolism (1150766, 3180341)
- Michael J. Fox Foundation for Parkinson’s Research (17303)
- FONDAP (15150012)
This publication has 157 references indexed in Scilit:
- Mlkl knockout mice demonstrate the indispensable role of Mlkl in necroptosisCell Research, 2013
- Necrostatin-1 analogues: critical issues on the specificity, activity and in vivo use in experimental disease modelsCell Death & Disease, 2012
- Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 KinaseCell, 2012
- The optic nerve head is the site of axonal transport disruption, axonal cytoskeleton damage and putative axonal regeneration failure in a rat model of glaucomaActa Neuropathologica, 2011
- Necrostatin-1 ameliorates symptoms in R6/2 transgenic mouse model of Huntington's diseaseCell Death & Disease, 2011
- cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent reactive oxygen species productionCell Death & Differentiation, 2010
- Clinical progression in Parkinson disease and the neurobiology of axonsAnnals of Neurology, 2010
- Phosphorylation-Driven Assembly of the RIP1-RIP3 Complex Regulates Programmed Necrosis and Virus-Induced InflammationCell, 2009
- Receptor Interacting Protein Kinase-3 Determines Cellular Necrotic Response to TNF-αCell, 2009
- Necrostatin-1 Reduces Histopathology and Improves Functional Outcome after Controlled Cortical Impact in MiceJournal of Cerebral Blood Flow & Metabolism, 2008