Non-canonical cell death in neurodegeneration: emerging mechanisms and therapeutic Frontiers - PubMed
6 days ago
- #therapeutics
- #cell-death
- #neurodegeneration
- Neurodegenerative diseases like Alzheimer's, Parkinson's, Huntington's, and ALS lack curative therapies and involve progressive neuronal loss.
- Non-canonical cell death pathways (ferroptosis, necroptosis, pyroptosis, parthanatos) contribute to neuroinflammation, oxidative stress, and mitochondrial dysfunction in neurodegeneration.
- Key regulatory proteins, triggers, and effectors of these pathways are discussed, along with their pathogenic roles.
- Pharmacological agents (e.g., ferrostatin-1, necrostatin-1, MCC950, PARP inhibitors) show neuroprotective effects in experimental studies.
- Clinical translation faces challenges like overlapping mechanisms, blood-brain barrier limitations, and safety concerns.
- Future strategies include biomarker-based patient stratification, multivalent interventions, and improved translational models.
- Targeting these pathways may offer new therapies to slow neurodegeneration progression.