Mitophagy: A promising therapeutic target for neuroprotection during ageing and age‐related diseases

British Journal of Pharmacology, Год журнала: 2023, Номер 180(12), С. 1542 - 1561

Опубликована: Фев. 16, 2023

Mitochondria and mitochondria-mediated signalling pathways are known to control synaptic signalling, as well long-lasting changes in neuronal structure function. Mitochondrial impairment is linked dysfunction normal ageing age-associated neurodegenerative ailments, including Parkinson's disease (PD) Alzheimer's (AD). Both proteolysis mitophagy perform a major role neuroprotection, by maintaining healthy mitochondrial population during ageing. Mitophagy, highly evolutionarily conserved cellular process, helps the clearance of damaged mitochondria thereby maintains metabolic balance, energy supply, survival health. Besides maintenance brain homeostasis, hippocampal also synapse formation, axonal development, dopamine release long-term depression. In contrast, defective contributes age-related neurodegeneration promoting accumulation leading dysfunction. Exercise, stress management, dynamics administering natural or synthetic pharmacological compounds some strategies used for neuroprotection neurological diseases. The current review discusses impact conditions, underlying molecular potential therapies based on recently elucidated mitophagy-inducing strategies.

Язык: Английский

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The pivotal role of JAK/STAT and IRS/PI3K signaling pathways in neurodegenerative diseases: Mechanistic approaches to polyphenols and alkaloids

Phytomedicine, Год журнала: 2023, Номер 112, С. 154686 - 154686

Опубликована: Янв. 31, 2023

Язык: Английский

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Identification of mitochondrial related signature associated with immune microenvironment in Alzheimer’s disease

Journal of Translational Medicine, Год журнала: 2023, Номер 21(1)

Опубликована: Июль 11, 2023

Abstract Background Alzheimer's disease (AD) is the most common neurodegenerative disease. Mitochondrial dysfunction and immune responses are important factors in pathogenesis of AD, but their crosstalk AD has not been studied. In this study, independent role interaction mitochondria-related genes cell infiltration were investigated using bioinformatics methods. Methods The datasets obtained from NCBI Gene Expression Omnibus (GEO), data mitochondrial was MitoCarta3.0 database. Subsequently, differential expression (DEGs) screening GSEA functional enrichment analysis performed. intersection DEGs related used to obtain MitoDEGs. MitoDEGs relevant determined by Least absolute shrinkage selection operator multiple support vector machine recursive feature elimination, as well protein–protein interactions (PPI) network random forest. 28 kinds cells analyzed ssGSEA, relationship between hub proportion levels verified models mice, OPA1 damage neuronal apoptosis investigated. Results functions pathways significantly enriched including response activation, IL1R pathway, metabolism, oxidative electron transport chain-oxphos system mitochondria. Hub closely based on PPI network, forest two learning algorithms. Five associated with neurological disorders identified biological function examination. found be correlated memory B cell, effector CD8 T activated dendritic natural killer type 17 helper Neutrophil, MDSC, plasmacytoid cell. These can also predict risk have good diagnostic efficacy. addition, mRNA BDH1, TRAP1, OPA1, DLD mice consistent results analysis, SPG7 showed a downward trend. Meanwhile, overexpression alleviated induced Aβ1-42. Conclusions potential identified. Their microenvironment may play crucial occurrence prognosis which provides new insight for studying exploring targets.

Язык: Английский

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Mitochondria in Aging and Alzheimer’s Disease: Focus on Mitophagy

The Neuroscientist, Год журнала: 2023, Номер 30(4), С. 440 - 457

Опубликована: Янв. 3, 2023

Alzheimer’s disease (AD) is characterized by the accumulation of amyloid β and phosphorylated τ protein aggregates in brain, which leads to loss neurons. Under microscope, function mitochondria uniquely primed play a pivotal role neuronal cell survival, energy metabolism, death. Research studies indicate that mitochondrial dysfunction, excessive oxidative damage, defective mitophagy neurons are early indicators AD. This review article summarizes latest development AD: 1) mechanism pathways, 2) importance functions, 3) metabolic pathways 4) link between dysfunction mechanisms AD, 5) potential mitochondrial-targeted therapeutics interventions treat patients with

Язык: Английский

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Oxidation of Quercetin and Kaempferol Markedly Amplifies Their Antioxidant, Cytoprotective, and Anti-Inflammatory Properties

Antioxidants, Год журнала: 2023, Номер 12(1), С. 155 - 155

Опубликована: Янв. 9, 2023

The contention that flavonoids' oxidation would necessarily lead to a loss of their antioxidant properties was recently challenged by the demonstration quercetin leads formation 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone (Que-BZF), metabolite whose potency notably higher than its precursor. Here, we compared and expanded former observation analogue kaempferol. Oxidation kaempferol led mixture metabolites included 2-(4-hydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone (Kae-BZF). Following chromatographic isolation Kae-BZF from such mixture, antioxidant, mitochondria- cell-protecting, NF-kB-inhibiting effects were assessed, with those Que-BZF, in Caco-2 cells exposed indomethacin as source ROS. concentrations Que-BZF (100 nm) (1 needed attain maximal protection 50- 5000-fold lower respective precursors. differences also seen when abilities inhibit indomethacin-induced activation NF-kB compared. These data not only reveal oxidative conversion into 2-benzoyl-2-hydroxy-3(2H)-benzofuranones (BZF) results considerable amplification original properties, but case kaempferol, is 100-fold greater quercetin.

Язык: Английский

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