Molecular and functional characteristics of receptor-interacting protein kinase 1 (RIPK1) and its therapeutic potential in Alzheimer's disease

Abstract

Inflammation and cell death processes positively control the organ homeostasis of an organism. Receptor-interacting protein kinase 1 (RIPK1), a member of the RIPK family, is a crucial regulator of cell death and inflammation, and control homeostasis at the cellular and tissue level. Necroptosis, a programmed form of necrosis-mediated cell death and tumor necrosis factor (TNF)-induced necrotic cell death, is mostly regulated by RIPK1 kinase activity. Thus, RIPK1 has recently emerged as an upstream kinase that controls multiple cellular pathways and participates in regulating inflammation and cell death. All the major cell types in the central nervous system (CNS) have been found to express RIPK1. Selective inhibition of RIPK1 has been shown to prevent neuronal cell death, which could ultimately lead to a significant reduction of neurodegeneration and neuroinflammation. In addition, the kinase structure of RIPK1 is highly conducive to the development of specific pharmacological small-molecule inhibitors. These factors have led to the emergence of RIPK1 as an important therapeutic target for Alzheimer's disease (AD).

Keywords: RIPK1; beta-amyloid; blood–brain barrier; neurodegeneration; neuroinflammation.