Novel insights into RIPK1 as a promising target for future Alzheimer’s disease treatment

Alzheimer's disease (AD) is an intractable neurodegenerative disease showing a clinical manifestation with memory loss, cognitive impairment and behavioral dysfunction. The predominant pathological characteristics of AD include neuronal loss, β-amyloid (Aβ) deposition and hyperphosphorylated Tau induced neurofibrillary tangles (NFTs), while considerable studies proved these could be triggered by neuronal death and neuroinflammation. Receptor-interacting protein kinase 1 (RIPK1) is a serine/threonine kinase existed at the cross-point of cell death and inflammatory signaling pathways. Emerging investigations have shed light on RIPK1 for its potential role in AD progression. The present review makes a bird's eye view on the functions of RIPK1 and mainly focus on the underlying linkages between RIPK1 and AD from comprehensive aspects including neuronal death, Aβ and Tau, inflammasome activation, BBB rupture, AMPK/mTOR, mitochondrial dysfunction and O-glcNAcylation. Moreover, the discovery of RIPK1 inhibitors, ongoing clinical trials along with future RIPK1-targeted therapeutics are also reviewed.