Cornel iridoid glycoside ameliorated Alzheimer's disease-like pathologies and necroptosis through RIPK1/MLKL pathway in young and aged SAMP8 mice

Abstract

Background Aging is an important risk factor for sporadic Alzheimer’s disease (AD) and other neurodegenerative diseases. Senescence-accelerated mouse-prone 8 (SAMP8) is used as an animal model for brain aging and sporadic AD researches. The aim of the current study was to investigate the pharmacological effects of cornel iridoid glycoside (CIG), an active ingredient of Cornus officinalis, on AD-type pathological changes in young and aged SAMP8 mice. Methods Nissl and immunohistochemical staining was applied to detect NeuN-labeled neurons and myelin basic protein-labeled myelin sheath,. Western blotting was used to detect the expression levels of related proteins of synapse, APP processing and necroptosis. Results The results showed that SAMP8 mice at the age of 6 and 14 months exhibited age-related neuronal loss, demyelination, synaptic damage, and APP amyloidogenic processing. In addition, the increased levels of receptor-interacting protein kinase-1 (RIPK1), mixed lineage kinase domain-like protein (MLKL) and p-MLKL indicating necroptosis were found in the brain of SAMP8 mice. Intragastric administration of CIG for 2 months alleviated neuronal loss and demyelination, increased the expression of synaptophysin, postsynaptic density protein 95 and AMPA receptor subunit 1, elevated the levels of soluble APPα fragment and a disintegrin and metalloproteinase 10 (ADAM10), and decreased the levels of RIPK1, p-MLKL and MLKL in the brain of young and aged SAMP8 mice. Conclusion This study denoted that CIG might be a potential drug for aging-associated neurodegenerative diseases such as AD.

Global Research Trends and Hotspots for Ferroptosis, Necroptosis, and Pyroptosis in Alzheimer’s Disease from the Past to 2023: A Combined Bibliometric Review

“…Of course, in addition to these two points, currently, numerous studies have evidenced necroptosis participates the involvement of necroptosis in AD pathology both in vitro and in vivo by neuronal death [22], blood-brain barrier damage [60], granulovacuolar degeneration [58], synaptic loss [61], restricted O-linked ␤-N-acetylglucosaminylation [62,63], and mitochondrial impairment [64], leading to subsequent cognitive impairment [57].…”

Cornel Iridoid Glycoside Ameliorated Alzheimer’s Disease-Like Pathologies and Necroptosis through RIPK1/MLKL Pathway in Young and Aged SAMP8 Mice

“…The preprint presentation of the manuscript [ 45 ] can be found at “ https://www.researchsquare.com/article/rs-230305/v1 .”…”