Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: May 2, 2023

Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on backbones amino acid side chains proteins and expand diversity proteins, which provides basis for emergence organismal complexity. To date, more than 650 types protein modifications, such as most well-known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short-chain long-chain acylation redox irreversible have been described, inventory is still increasing. By changing conformation, localization, activity, stability, charges, interactions with other biomolecules, PTMs ultimately alter phenotypes biological processes cells. The homeostasis important human health. Abnormal may cause changes in properties loss functions, are closely related occurrence development various diseases. In this review, we systematically introduce characteristics, regulatory mechanisms, functions health addition, therapeutic prospects diseases by targeting associated enzymes also summarized. This work will deepen understanding promote discovery diagnostic prognostic markers drug targets

Language: Английский

---

Mitochondria: It is all about energy

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 14

Published: April 25, 2023

Mitochondria play a key role in both health and disease. Their function is not limited to energy production but serves multiple mechanisms varying from iron calcium homeostasis the of hormones neurotransmitters, such as melatonin. They enable influence communication at all physical levels through interaction with other organelles, nucleus, outside environment. The literature suggests crosstalk between mitochondria circadian clocks, gut microbiota, immune system. might even be hub supporting integrating activity across these domains. Hence, they (missing) link Mitochondrial dysfunction related metabolic syndrome, neuronal diseases, cancer, cardiovascular infectious inflammatory disorders. In this regard, diseases Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS), chronic fatigue syndrome (CFS), pain are discussed. This review focuses on understanding mitochondrial action that allow for maintenance pathways toward dysregulated mechanisms. Although have allowed us adapt changes over course evolution, turn, evolution has shaped mitochondria. Each evolution-based intervention influences its own way. use physiological stress triggers tolerance stressor, achieving adaptability resistance. describes strategies could recover functioning providing comprehensive, root-cause-focused, integrative approach recovering treating people suffering diseases.

Language: Английский

---

Progress in Understanding Oxidative Stress, Aging, and Aging-Related Diseases

Antioxidants, Journal Year: 2024, Volume and Issue: 13(4), P. 394 - 394

Published: March 25, 2024

Under normal physiological conditions, reactive oxygen species (ROS) are produced through redox reactions as byproducts of respiratory and metabolic activities. However, due to various endogenous exogenous factors, the body may produce excessive ROS, which leads oxidative stress (OS). Numerous studies have shown that OS causes a variety pathological changes in cells, including mitochondrial dysfunction, DNA damage, telomere shortening, lipid peroxidation, protein modification, all can trigger apoptosis senescence. also induces aging-related diseases, such retinal disease, neurodegenerative osteoarthritis, cardiovascular cancer, ovarian prostate disease. In this review, we aim introduce multiple internal external triggers mediate ROS levels rodents humans well relationship between OS, aging, diseases. Finally, present statistical analysis effective antioxidant measures currently being developed applied field aging research.

Language: Английский

---

Metformin decelerates aging clock in male monkeys

Cell, Journal Year: 2024, Volume and Issue: 187(22), P. 6358 - 6378.e29

Published: Sept. 12, 2024

Language: Английский

---

Nebulized Glutathione as a Key Antioxidant for the Treatment of Oxidative Stress in Neurodegenerative Conditions

Nutrients, Journal Year: 2024, Volume and Issue: 16(15), P. 2476 - 2476

Published: July 31, 2024

Glutathione (GSH), a tripeptide synthesized intracellularly, serves as pivotal antioxidant, neutralizing reactive oxygen species (ROS) and nitrogen (RNS) while maintaining redox homeostasis detoxifying xenobiotics. Its potent antioxidant properties, particularly attributed to the sulfhydryl group (-SH) in cysteine, are crucial for cellular health across various organelles. The glutathione-glutathione disulfide (GSH-GSSG) cycle is facilitated by enzymes like glutathione peroxidase (GPx) reductase (GR), thus aiding detoxification processes mitigating oxidative damage inflammation. Mitochondria, being primary sources of species, benefit significantly from GSH, which regulates metal supports autophagy, apoptosis, ferroptosis, playing fundamental role neuroprotection. vulnerability brain stress underscores importance GSH neurological disorders regenerative medicine. Nebulization presents novel promising approach delivering this directly central nervous system (CNS), potentially enhancing its bioavailability therapeutic efficacy. This method may offer significant advantages neurodegeneration nuclear factor erythroid 2-related 2 (NRF2) pathway signaling mitochondrial function, thereby providing direct By addressing detrimental effects on neuronal health, nebulized could play managing ameliorating conditions such Parkinson's Disease (PD) Alzheimer's (AD). Further clinical research warranted elucidate potential preserving CNS combating neurodegenerative conditions, aiming improve outcomes individuals affected diseases characterized neuroinflammation.

Language: Английский

---

Mechanisms of Ferroptosis and Emerging Links to the Pathology of Neurodegenerative Diseases

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: June 28, 2022

Neurodegenerative diseases are a diverse class of attributed to chronic progressive neuronal degeneration and synaptic loss in the brain and/or spinal cord, including Alzheimer’s disease, Parkinson’s Huntington’s amyotrophic lateral sclerosis multiple sclerosis. The pathogenesis neurodegenerative is complex diverse, often involving mitochondrial dysfunction, neuroinflammation, epigenetic changes. However, has not been fully elucidated. Recently, accumulating evidence revealed that ferroptosis, newly discovered iron-dependent lipid peroxidation-driven type programmed cell death, provides another explanation for occurrence progression diseases. Here, we provide an overview process regulation mechanisms summarize current research progresses support contribution ferroptosis A comprehensive understanding emerging roles will shed light on development novel therapeutic technologies strategies slowing down these

Language: Английский

---

Autophagic lysosome reformation in health and disease

Autophagy, Journal Year: 2022, Volume and Issue: 19(5), P. 1378 - 1395

Published: Nov. 21, 2022

Lysosomes are the primary degradative compartment within cells and there have been significant advances over past decade toward understanding how lysosome homeostasis is maintained. Lysosome repopulation ensures sustained autophagy function, a fundamental process that protects against disease. During macroautophagy/autophagy, cellular debris sequestered into phagophores mature autophagosomes, which then fuse with lysosomes to generate autolysosomes in contents degraded. Autophagy cannot proceed without sufficient generation of lysosomes, this can be achieved via their de novo biogenesis. Alternatively, during autophagic reformation (ALR), generated recycling autolysosome membranes. process, undergo membrane remodeling scission fragments, functional lysosomes. By utilizing membranes already formed autophagy, facilitates an efficient pathway for re-deriving particularly under conditions prolonged flux. ALR dysfunction emerging as important disease mechanism including neurodegenerative disorders such hereditary spastic paraplegia Parkinson disease, neuropathies Charcot-Marie-Tooth storage disorders, muscular dystrophy, metabolic syndrome, inflammatory liver disorders. Here, we provide comprehensive review ALR, overview its dynamic spatiotemporal regulation by MTOR phosphoinositides, role plays many diseases.

Language: Английский

---

Normal and Pathological NRF2 Signalling in the Central Nervous System

Antioxidants, Journal Year: 2022, Volume and Issue: 11(8), P. 1426 - 1426

Published: July 22, 2022

The nuclear factor erythroid 2-related 2 (NRF2) was originally described as a master regulator of antioxidant cellular response, but in the time since, numerous important biological functions linked to cell survival, detoxification, metabolism, autophagy, proteostasis, inflammation, immunity, and differentiation have been attributed this pleiotropic transcription that regulates hundreds genes. After 40 years in-depth research key discoveries, NRF2 is now at center vast regulatory network, revealing signalling increasingly complex. It widely recognized reactive oxygen species (ROS) play role human physiological pathological processes such ageing, obesity, diabetes, cancer, neurodegenerative diseases. high consumption associated with levels free iron oxidizable unsaturated lipids make brain particularly vulnerable oxidative stress. A good stability activity thus crucial maintain redox balance therefore homeostasis. In review, we gathered recent data about contribution pathway healthy well during metabolic diseases, ageing-related We also discuss promising therapeutic strategies need for better understanding cell-type-specific these different fields.

Language: Английский

---

Oxygen metabolism abnormality and Alzheimer's disease: An update

Redox Biology, Journal Year: 2023, Volume and Issue: 68, P. 102955 - 102955

Published: Nov. 8, 2023

Oxygen metabolism abnormality plays a crucial role in the pathogenesis of Alzheimer's disease (AD) via several mechanisms, including hypoxia, oxidative stress, and mitochondrial dysfunction. Hypoxia condition usually results from living high-altitude habitat, cardiovascular cerebrovascular diseases, chronic obstructive sleep apnea. Chronic hypoxia has been identified as significant risk factor for AD, showing an aggravation various pathological components such amyloid β-protein (Aβ) metabolism, tau phosphorylation, dysfunction, neuroinflammation. It is known that excessive hyperoxia can both result stress Oxidative dysfunction increase Aβ proteins lead to redox imbalance, thus forming vicious cycle exacerbating AD pathology. Hyperbaric oxygen therapy (HBOT) non-invasive intervention its capacity significantly enhance cerebral oxygenation levels, which attenuate aggregation, However, further investigation imperative determine optimal pressure, duration exposure, frequency HBOT sessions. In this review, we explore prospects with aim enhancing our understanding underlying molecular mechanisms AD. Current research aimed at attenuating abnormalities holds promise providing novel therapeutic approaches

Language: Английский

---

Activators of Nrf2 to Counteract Neurodegenerative Diseases

Antioxidants, Journal Year: 2023, Volume and Issue: 12(3), P. 778 - 778

Published: March 22, 2023

Neurodegenerative diseases are incurable and debilitating conditions that result in progressive degeneration loss of nerve cells. Oxidative stress has been proposed as one factor plays a potential role the pathogenesis neurodegenerative disorders since neuron cells particularly vulnerable to oxidative damage. Nuclear (erythroid-derived 2)-like 2 (Nrf2) is strictly related anti-inflammatory antioxidative cell response; therefore, its activation consequent enhancement cellular pathways have therapeutic approach. Several Nrf2 activators with different mechanisms diverse structures reported, but those applied for neurodisorders still limited. However, very last few years, interesting progress made, enhancing blood–brain barrier penetration, make effective drugs, designing Nrf2-based multitarget-directed ligands affect multiple involved pathology diseases. The present review gives an overview most representative findings this research area.

Language: Английский

---