PANoptosis: Potential Therapeutic Prospects in Alzheimer's Disease

Abstract

Alzheimer's disease (AD), a progressive neurodegenerative disorder, constitutes a major global health burden with escalating socioeconomic costs. The precise pathophysiological cascades and etiological underpinnings of AD remain incompletely elucidated. Current amyloid-beta (Aβ)–targeted therapies demonstrate limited clinical efficacy and significant adverse effects, prompting reevaluation of therapeutic development strategies. This therapeutic impasse underscores the imperative to investigate novel pathogenic pathways and identify viable molecular targets. PANoptosis, a coordinated cell death mechanism integrating pyroptosis, apoptosis, and necroptosis, has emerged as a pathophysiological nexus in diverse conditions spanning infectious diseases, malignancies, and chronic inflammatory disorders. Fundamentally, universal apoptosis represents a holistic framework. The integration of these key components generates a novel conceptualization, with all elements being indispensable. The absence of any one element precludes the formation of PANoptosis. Direct evidence that PANoptosis regulates AD pathogenesis is currently lacking. This review synthesizes current understanding of PANoptosis molecular drivers and evaluates their potential mechanistic contributions to AD pathogenesis, proposing a framework for developing possible targeted neuroprotective strategies.