Total recall: the role of PIDDosome components in neurodegeneration

The PIDDosome is a multiprotein complex that includes p53-induced protein with a death domain 1 (PIDD1), receptor-interacting protein-associated ICH-1/ CED-3 homologous protein with a death domain (RAIDD), and caspase-2, the ac-tivation of which is driven by PIDDosome assembly. In addition to the key role of the PIDDosome in the regulation of cell differentiation, tissue homeostasis, and organogenesis and regeneration, caspase-2, RAIDD and PIDD1 engagement in neuronal development was shown. Here, we focus on the involvement of PIDDosome components in neurodegenerative disorders, including retinal neu-ropathies, different types of brain damage, and Alzheimer's disease (AD), Huntington's disease (HD), and Lewy body disease. We also discuss pathogenic variants of PIDD1, RAIDD, and caspase-2 that are associated with intellectual, behavioral, and psychological abnormalities, together with prospective PIDDosome inhibition strategies and their potential clinical application.

Automated summary

The PIDDosome is a multiprotein complex that plays important roles in cellular processes and neurodevelopment. This article focuses on the involvement of PIDDosome components in neurodegenerative disorders, as well as pathogenic variants and potential therapeutic strategies.