In the human body, cell division and metabolism are expected to transpire uneventfully for approximately 25 years. Then, secondary metabolism and cell damage products accumulate, and ageing phenotypes are acquired, causing the progression of disease. Among these age-related diseases, neurodegenerative diseases have attracted considerable attention because of their irreversibility, the absence of effective treatment and their relationship with social and economic pressures. Mechanistic (formerly mammalian) target of rapamycin (mTOR), sirtuin (SIRT) and insulin/insulin growth factor 1 (IGF1) signalling pathways are among the most important pathways in ageing-associated conditions, such as neurodegeneration. These longevity-related pathways are associated with a diversity of various processes, including metabolism, cognition, stress reaction and brain plasticity. In this review, we discuss the roles of sirtuin and mTOR in ageing and neurodegeneration, with an emphasis on their regulation of autophagy, apoptosis and mitochondrial energy metabolism. The intervention of neurodegeneration using potential antioxidants, including vitamins, phytochemicals, resveratrol, herbals, curcumin, coenzyme Q10 and minerals, specifically aimed at retaining mitochondrial function in the treatment of Alzheimer's disease, Parkinson's disease and Huntington's disease is highlighted.
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http://dx.doi.org/10.1007/s12035-020-02083-1 | DOI Listing |
Antioxidants (Basel)
January 2025
Institute of Clinical Physiology, National Research Council, Via Moruzzi 1, 56124 Pisa, Italy.
Cellular senescence is a state of permanent cell cycle arrest accompanied by metabolic activity and characteristic phenotypic changes. This process is crucial for developing age-related diseases, where excessive calorie intake accelerates metabolic dysfunction and aging. Overnutrition disturbs key metabolic pathways, including insulin/insulin-like growth factor signaling (IIS), the mammalian target of rapamycin (mTOR), and AMP-activated protein kinase.
View Article and Find Full Text PDFPharmaceuticals (Basel)
December 2024
Department of Pharmacology, Egyptian Drug Authority (EDA)-Formerly NODCAR, Giza 12654, Egypt.
The antioxidant/antiapoptotic features of dapagliflozin (DPG) have mediated its beneficial actions against several experimental models. However, no studies have been conducted to determine whether DPG mitigates the renal injury triggered by cadmium (Cd). Herein, DPG was studied for its potential to attenuate kidney damage in Cd-intoxicated rats, as well as to unravel the mechanisms involving oxidative events, autophagy, and apoptosis.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China. Electronic address:
The sirtuin (SIRT) family is a group of seven conserved nicotinamide adenine dinucleotide-dependent histone deacetylases (SIRT1-SIRT7), which play crucial roles in various fundamental biological processes, including metabolism, aging, stress responses, inflammation, and cell survival. The role of SIRTs in neuro-pathophysiology has recently attracted significant attention. Notably, SIRT1-SIRT3 have been identified as key players in neuroprotection as they reduce neuroinflammation and regulate mitochondrial function.
View Article and Find Full Text PDFPhysiol Genomics
December 2024
Experimental Medicine Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, 11481, Saudi Arabia.
This study investigates the molecular responses to heat stroke in young and old patients by comparing whole-genome transcriptomes between age groups. We analyzed transcriptomic profiles from patients categorized into two age-defined cohorts: young (mean age = 44.9 ± 6 years) and old (mean age = 66.
View Article and Find Full Text PDFInt Immunopharmacol
January 2025
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Sinai University- Arish Branch, Arish 45511, Egypt.
Unlabelled: Despite a deep understanding of Parkinson's disease (PD) and levodopa-induced dyskinesia (LID) pathogenesis, current therapies are insufficient to effectively manage the progressive nature of PD or halt LID. Growing hypotheses suggested the NOD-like receptor 3 (NLRP3) inflammasome and orphan nuclear receptor-related 1 (Nurr1)/glycogen synthase kinase-3β (GSK-3β) and peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α)/sirtuin 3 (SIRT3) pathways as potential avenues for halting neuroinflammation and oxidative stress in PD.
Aims: This study investigated for the first time the neuroprotective effect of canagliflozin against PD and LID in rotenone-intoxicated rats, emphasizing the crosstalk among the NLRP3/caspase-1 cascade, PGC-1α/SIRT3 pathway, mammalian target of rapamycin (mTOR)/beclin-1, and Nurr1/β-catenin/GSK-3β pathways as possible treatment strategies in PD and LID.
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