Toxicology and Applied Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 117237 - 117237
Published: Jan. 1, 2025
Language: Английский
Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 211, P. 115522 - 115522
Published: March 28, 2023
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases that affect millions people worldwide, with both prevalence and incidence increasing age. It characterized by cognitive decline associated, specifically, degeneration cholinergic neurons. The problem this even more fundamental as available therapies remain fairly limited mainly focused on symptoms' relief. Although aetiology remains elusive, two main pathological hallmarks are described: i) presence neurofibrillary tangles formed unfolded protein aggregates (hyperphosphorylated Tau protein) ii) extracellular amyloid-beta peptide. Given complexity surrounding pathogenesis disease, several potential targets have been highlighted interrelated upon its progression, such oxidative stress accumulation metal ions. Thus, advances made development innovative multitarget therapeutical compounds to delay progression restore cell function. This review focuses ongoing research new insights emerging disease-modifying drugs for AD treatment. Furthermore, classical novel biomarkers early diagnosis their role in assisting improvement targeted will also be approached.
Language: Английский
Citations
113
Phytomedicine, Journal Year: 2023, Volume and Issue: 126, P. 154887 - 154887
Published: May 20, 2023
Language: Английский
Citations
54
Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116512 - 116512
Published: April 3, 2024
GPX4 (Glutathione peroxidase 4) serves as a crucial intracellular regulatory factor, participating in various physiological processes and playing significant role maintaining the redox homeostasis within body. Ferroptosis, form of iron-dependent non-apoptotic cell death, has gained considerable attention recent years due to its involvement multiple pathological processes. is closely associated with ferroptosis functions primary inhibitor this process. Together, contribute pathophysiology several diseases, including sepsis, nervous system ischemia reperfusion injury, cardiovascular cancer. This review comprehensively explores roles impacts development progression these aim providing insights for identifying potential therapeutic strategies future.
Language: Английский
Citations
51
Trends in Pharmacological Sciences, Journal Year: 2023, Volume and Issue: 44(10), P. 674 - 688
Published: Aug. 30, 2023
Language: Английский
Citations
49
Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116112 - 116112
Published: Jan. 2, 2024
Ferroptosis is a newly identified form of non-apoptotic programmed cell death, characterized by the iron-dependent accumulation lethal lipid reactive oxygen species (ROS) and peroxidation membrane polyunsaturated fatty acid phospholipids (PUFA-PLs). unique among other death modalities in many aspects. It initiated excessive oxidative damage due to iron overload compromised antioxidant defense systems, including system Xc-/ glutathione (GSH)/glutathione peroxidase 4 (GPX4) pathway GPX4-independent pathways. In past ten years, ferroptosis was reported play critical role pathogenesis various cardiovascular diseases, e.g., atherosclerosis (AS), arrhythmia, heart failure, diabetic cardiomyopathy, myocardial ischemia-reperfusion injury. Studies have dysfunctional metabolism abnormal expression profiles ferroptosis-related factors, iron, GSH, GPX4, ferroportin (FPN), SLC7A11 (xCT), as indicators for atherogenesis. Moreover, plaque cells, i.e., vascular endothelial (VEC), macrophage, smooth muscle (VSMC), positively correlate with atherosclerotic development. Many macromolecules, drugs, Chinese herbs, food extracts can inhibit atherogenic process suppressing cells. contrast, some inducers significant pro-atherogenic effects. However, mechanisms through which affects progression AS still need be well-known. This review summarizes molecular their emerging AS, aimed at providing novel, promising druggable targets anti-AS therapy.
Language: Английский
Citations
35
Acta Neuropathologica, Journal Year: 2024, Volume and Issue: 147(1)
Published: April 7, 2024
Language: Английский
Citations
22
Pharmacological Research, Journal Year: 2024, Volume and Issue: 206, P. 107258 - 107258
Published: June 21, 2024
Several cardiovascular illnesses are associated with aberrant activation of cellular pyroptosis, ferroptosis, necroptosis, cuproptosis, disulfidptosis and macrophage polarisation as hallmarks contributing to vascular damage abnormal cardiac function. Meanwhile, these three novel forms dysfunction closely related mitochondrial homeostasis. Mitochondria the main organelles that supply energy maintain Mitochondrial stability is maintained through a series regulatory pathways, such fission, fusion mitophagy. Studies have shown (e.g., impaired dynamics mitophagy) promotes ROS production, leading oxidative stress, which induces M1 phenotypic polarisation. Therefore, an in-depth knowledge dynamic regulation mitochondria during necessary understand disease development. This paper systematically summarises impact changes in mitophagy on regulating dysfunctions promote understanding pathogenesis diseases provide corresponding theoretical references for treating diseases.
Language: Английский
Citations
20
Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 196, P. 106505 - 106505
Published: April 19, 2024
Alzheimer's and Parkinson's diseases are two of the most frequent neurological diseases. The clinical features AD memory decline cognitive dysfunction, while PD mainly manifests as motor dysfunction such limb tremors, muscle rigidity abnormalities, slow gait. Abnormalities in cholesterol, sphingolipid, glycerophospholipid metabolism have been demonstrated to directly exacerbate progression by stimulating Aβ deposition tau protein tangles. Indirectly, abnormal lipids can increase burden on brain vasculature, induce insulin resistance, affect structure neuronal cell membranes. Abnormal lipid leads through inducing accumulation α-syn, mitochondria endoplasmic reticulum, ferroptosis. Great progress has made targeting abnormalities for treatment recent years, like metformin, insulin, peroxisome proliferator-activated receptors (PPARs) agonists, monoclonal antibodies apolipoprotein E (ApoE). This review comprehensively summarizes involvement dysregulated pathogenesis PD, application Lipid Monitoring, emerging regulatory drug targets. A better understanding lipidological bases may pave way developing effective prevention methods neurodegenerative disorders.
Language: Английский
Citations
16
Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)
Published: Jan. 29, 2025
Ferroptosis is a form of iron-dependent programmed cell death, which distinct from apoptosis, necrosis, and autophagy. Mitochondria play critical role in initiating amplifying ferroptosis cancer cells. Voltage-Dependent Anion Channel 1 (VDAC1) embedded the mitochondrial outer membrane, exerts roles regulation ferroptosis. However, mechanisms VDAC1 oligomerization regulating are not well elucidated. Here, we identify that binding protein V-Set Transmembrane Domain Containing 2 Like (VSTM2L), mainly localized to mitochondria, positively associated with prostate (PCa) progression, key regulator Moreover, VSTM2L knockdown PCa cells enhances sensitivity RSL3-induced Mechanistically, forms complex hexokinase (HK2), enhancing their affinity preventing oligomerization, thereby inhibiting maintaining mitochondria homeostasis vitro vivo. Collectively, our findings reveal pivotal for mitochondria-localized driving resistance highlight its potential as ferroptosis-inducing therapeutic target treatment PCa.
Language: Английский
Citations
2
Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 61(3), P. 1507 - 1526
Published: Sept. 19, 2023
Language: Английский
Citations
26