Molecular mechanism and potential therapeutic targets of necroptosis and ferroptosis in Alzheimer's disease - 11/11/23
Abstract |
Alzheimer's disease (AD), a neurodegenerative condition, is defined by neurofibrillary tangles, amyloid plaques, and gradual cognitive decline. Regardless of the advances in understanding AD's pathogenesis and progression, its causes are still contested, and there are currently no efficient therapies for the illness. The post-mortem analyses revealed widespread neuronal loss in multiple brain regions in AD, evidenced by a decrease in neuronal density and correlated with the disease's progression and cognitive deterioration. AD's neurodegeneration is complicated, and different types of neuronal cell death, alone or in combination, play crucial roles in this process. Recently, the involvement of non-apoptotic programmed cell death in the neurodegenerative mechanisms of AD has received a lot of attention. Aberrant activation of necroptosis and ferroptosis, two newly discovered forms of regulated non-apoptotic cell death, is thought to contribute to neuronal cell death in AD. In this review, we first address the main features of necroptosis and ferroptosis, cellular signaling cascades, and the mechanisms involved in AD pathology. Then, we discuss the latest therapies targeting necroptosis and ferroptosis in AD animal/cell models and human research to provide vital information for AD treatment.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Necroptosis and ferroptosis are non-apoptotic forms of programmed cell death. |
• | Necroptosis and ferroptosis promote AD progression through known mechanisms. |
• | Ferroptosis triggers necroptosis in AD, making neurons susceptible to cell death. |
• | Ferroptosis and necroptosis-inhibiting agents provide therapeutic options for AD. |
Abbreviations : AD, EOAD, LOAD, APP, AICD, Aβ, Aβo, APOE4, MCI, NFTs, CTF, PCD, NCCD, TNF, TRAIL, ROS, L-ROS, DAMPs, TLRs, PRRs, MLKL, RIPK, RHIM, TNFR1, TRAF2, TRAF5, TRADD, LUBAC, cIAPs, TAK1, TABs, NF-κB, IKK, NEMO, CYLD, FADD, GVD, Nec-1, IL-1β, IL-6, Al, AlCl3, AAV, CSF, CNS, PBMCs, RAS, GSH, GPX4, DMT1, Fpn, Tf, TfR1, STEAP3, LIP, NCOA4, AA, AdA, CoA, ACSL4, PE, LPCAT3, LOXs, FSP1, NADP+, CoQ10, GSSG, PUFAs, D-PUFA, GCL, GSS, MVA, Acetyl-CoA, HMG-CoA, IPP, Sec, Se, AIFM2, NBIA, IREB2, ACSF2, MAPK, CDK5, GSK-3, IRP, IRE, DFO, LA, 4-HNE, Fer-1, Lip-1, GCEE, GSTO, Grsf1, Se-Met, Se-yeast, NRF2
Keywords : Necroptosis, Ferroptosis, Neurodegeneration, Alzheimer's disease
Plan
Vol 168
Article 115656- décembre 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?