PANoptosis: Potential Therapeutic Prospects in Alzheimer's Disease
1Department of Endocrinology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
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.
Insights
Alzheimer's disease (AD) may involve PANoptosis, a cell death process integrating pyroptosis, apoptosis, and necroptosis. Investigating PANoptosis offers new neuroprotective strategies for AD.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder with significant global health and socioeconomic impact.
- Current amyloid-beta (Aβ)-targeted therapies for AD show limited efficacy and notable adverse effects.
- The exact causes and pathological mechanisms of AD are not fully understood, necessitating new therapeutic targets.
Purpose of the Study:
- To review the molecular drivers of PANoptosis, a programmed cell death pathway.
- To evaluate the potential role of PANoptosis in Alzheimer's disease pathogenesis.
- To propose novel neuroprotective strategies targeting PANoptosis in AD.
Main Methods:
- Literature review synthesizing current knowledge on PANoptosis.
- Analysis of molecular mechanisms underlying PANoptosis.
- Evaluation of potential links between PANoptosis and AD pathology.
Main Results:
- PANoptosis is a coordinated cell death mechanism involving pyroptosis, apoptosis, and necroptosis.
- While direct evidence is lacking, PANoptosis pathways are implicated in various diseases.
- This review proposes PANoptosis as a potential key player in AD pathogenesis.
Conclusions:
- PANoptosis represents a novel conceptual framework for understanding cell death.
- Targeting PANoptosis may offer new therapeutic avenues for Alzheimer's disease.
- Further research is needed to elucidate the direct role of PANoptosis in AD and develop targeted interventions.
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