DAMPs and neurodegeneration

Abstract

The concept of neuroinflammation has come a full circle; from being initially regarded as a controversial viewpoint to its present day acceptance as an integral component of neurodegenerative processes. A closer look at the etiopathogenesis of many neurodegenerative conditions will reveal a patho-symbiotic relationship between neuroinflammation and neurodegeneration, where the two liaise with each other to form a self-sustaining vicious cycle that facilitates neuronal demise. Here, we focus on damage associated molecular patterns or DAMPs as a potentially important nexus in the context of this lethal neuroinflammation-neurodegeneration alliance. Since their nomenclature as "DAMPs" about a decade ago, these endogenous moieties have consistently been reported as novel players in sterile (non-infective) inflammation. However, their roles in inflammatory responses in the central nervous system (CNS), especially during chronic neurodegenerative disorders are still being actively researched. The aim of this review is to first provide a general overview of the neuroimmune response in the CNS within the purview of DAMPs, its receptors and downstream signaling. This is then followed by discussions on some of the DAMP-mediated neuroinflammatory responses involved in chronic neurodegenerative diseases. Along the way, we also highlighted some important gaps in our existing knowledge regarding the role of DAMPs in neurodegeneration, the clarification of which we believe would aid in the prospects of developing treatment or screening strategies directed at these molecules.

Keywords: DAMPs; Inflammasomes; Neurodegeneration; Neuroinflammation; PRRs.