Journal Article

Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases

Yuan, Junying, Ofengeim, Dimitry, Amin, Palak

2019

Overview

Apoptosis is crucial for the normal development of the nervous system, whereas neurons in the adult CNS are relatively resistant to this form of cell death. However, under pathological conditions, upregulation of death receptor family ligands, such as tumour necrosis factor (TNF), can sensitize cells in the CNS to apoptosis and a form of regulated necrotic cell death known as necroptosis that is mediated by receptor-interacting protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain-like protein (MLKL). Necroptosis promotes further cell death and neuroinflammation in the pathogenesis of several neurodegenerative diseases, including multiple sclerosis, amyotrophic lateral sclerosis, Parkinson disease and Alzheimer disease. In this Review, we outline the evidence implicating necroptosis in these neurological diseases and suggest that targeting RIPK1 might help to inhibit multiple cell death pathways and ameliorate neuroinflammation.

• Publisher: Nature Publishing Group
• Subject: Alzheimer's disease / Amyotrophic lateral sclerosis / Apoptosis / Cell death / Central nervous system / Inflammation / Kinases / MAP kinase / Movement disorders / Multiple sclerosis / Necroptosis / Neurodegenerative diseases / Neurological diseases / Parkinson's disease / Protein kinase / Tumor necrosis factor / Tumor necrosis factor-TNF / Tumors