PANoptosis in Alzheimer's disease: The expanding landscape of programmed cell death mechanisms and therapeutic interventions - PubMed
3 hours ago
- #Alzheimer's disease
- #PANoptosis
- #neurodegeneration
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia in elderly people.
- PANoptosis, a lytic form of programmed cell death integrating pyroptosis, apoptosis, and necroptosis, is a central driver of AD progression.
- PANoptosis is orchestrated by multiprotein PANoptosome complexes such as RIPK1, AIM2, ZBP1, and NLRP12.
- In AD, Aβ and tau aggregates activate inflammasomes, trigger mitochondrial dysfunction, oxidative stress, and chronic neuroinflammation, leading to PANoptotic cell death.
- Dysregulation of signaling pathways like cGAS-STING, PI3K/AKT, JAK/STAT/IRF1, and p38/ERK/JNK MAPK contributes to PANoptosis.
- Preclinical studies and clinical trials suggest neuroprotective potential of compounds and drugs targeting PANoptotic pathways.
- This review highlights PANoptosis as a critical pathological mechanism in AD and explores therapeutic interventions to disrupt this cell death program.