Oxidative Stress Occurs Prior to Amyloid Aβ Plaque Formation and Tau Phosphorylation in Alzheimer’s Disease: Role of Glutathione and Metal Ions

ACS Chemical Neuroscience, Journal Year: 2023, Volume and Issue: 14(17), P. 2944 - 2954

Published: Aug. 10, 2023

Alzheimer's disease (AD) is an insidious and progressive neurodegenerative disorder that affects millions of people worldwide. Although the pathogenesis remains obscure, there are two dominant causal hypotheses. Since last three decades, amyloid beta (Aβ) deposition was most prominent hypothesis, other tau hyperphosphorylation hypothesis. The confirmed diagnostic criterion for AD presence neurofibrillary tangles (NFTs) composed hyperphosphorylated toxic oligomeric Aβ in autopsied brain. Consistent with these hypotheses, oxidative stress (OS) garnering major attention research. OS results from imbalance pro-oxidants antioxidants. There a considerable debate scientific community on which process occurs first, or plaque deposition/tau hyperphosphorylation. Based recent observations various laboratories including ours along critical analysis those information, we believe early event leads to as well dimerization protein its subsequent This hypothesis immediately suggests consideration novel therapeutic approaches include antioxidants involving glutathione enrichment brain by supplementation without iron chelator.

Language: Английский

---

The neuroprotective effects of targeting key factors of neuronal cell death in neurodegenerative diseases: The role of ER stress, oxidative stress, and neuroinflammation

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: March 6, 2023

Neuronal loss is one of the striking causes various central nervous system (CNS) disorders, including major neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), and Amyotrophic lateral sclerosis (ALS). Although these diseases have different features clinical manifestations, they share some common mechanisms pathology. Progressive regional neurons in patients responsible for motor, memory, cognitive dysfunctions, leading to disabilities death. cell death linked pathways conditions. Protein misfolding aggregation, mitochondrial dysfunction, generation reactive oxygen species (ROS), activation innate immune response are most critical hallmarks diseases. Thus, endoplasmic reticulum (ER) stress, oxidative neuroinflammation pathological factors neuronal Even though exact not fully discovered, notable role mentioned well known. On this basis, researchers been prompted investigate neuroprotective effects targeting underlying determine a promising therapeutic approach treatment. This review provides an overview ER death, mainly discussing or molecules involved factors.

Language: Английский

---

Ionic liquids revolutionizing biomedicine: recent advances and emerging opportunities

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(20), P. 7262 - 7293

Published: Jan. 1, 2023

This review highlights the recent advances and emerging opportunities of ionic liquids in biomedicine based on their intrinsic advantages potentials.

Language: Английский

---

Myelin in Alzheimer’s disease: culprit or bystander?

Acta Neuropathologica Communications, Journal Year: 2023, Volume and Issue: 11(1)

Published: March 31, 2023

Alzheimer's disease (AD) is a neurodegenerative disorder with neuronal and synaptic losses due to the accumulation of toxic amyloid β (Αβ) peptide oligomers, plaques, tangles containing tau (tubulin-associated unit) protein. While familial AD caused by specific mutations, sporadic more common appears result from complex chronic brain neuroinflammation mitochondriopathies, inducing free radicals' accumulation. In aged brain, mutations in DNA several unfolded proteins participate amyloidosis response effect on myelin sheath axons, leading cognitive deficits dementia. Αβ peptides are most frequent form oligomers. Accumulations misfolded during years alters different metabolic mechanisms, induce inflammatory immune responses consequences cells. Myelin composition architecture may appear be an early target for activity Aβ others hydrophobic proteins. this work, we describe possible role alterations genesis onset symptomatology. We propose that some pathophysiological clinical forms arise structural disorders processes myelination/demyelination regions where non-functional important. these forms, primacy deleterious would matter questioning initiating neuropathology primarily fact dysmyelination.

Language: Английский

---

Neuromodulatory effect of vardenafil on aluminium chloride/d-galactose induced Alzheimer’s disease in rats: emphasis on amyloid-beta, p-tau, PI3K/Akt/p53 pathway, endoplasmic reticulum stress, and cellular senescence

Inflammopharmacology, Journal Year: 2023, Volume and Issue: 31(5), P. 2653 - 2673

Published: July 17, 2023

Abstract Dysregulation of protein homeostasis, proteostasis, is a distinctive hallmark many neurodegenerative disorders and aging. Deleteriously, the accumulation aberrant proteins in Alzheimer’s disease (AD) accompanied with marked collapse proteostasis network. The current study explored potential therapeutic effect vardenafil (VAR), phosphodiesterase-5 inhibitor, AlCl 3 / d -galactose ( -gal)-induced AD rats its possible underlying mechanisms. impact VAR treatment on neurobehavioral function, hippocampal tissue architecture, activity cholinergic system main enzymes were assessed utilizing at doses 0.3 mg/kg 1 mg/kg. Additionally, expression level amyloid-beta phosphorylated tau hippocampus figured out. Accordingly, higher dose was selected to contemplate Intriguingly, elevated cyclic guanosine monophosphate averted repressed proteasome by -gal; hence, might alleviate burden toxic aggregates AD. In addition, substantial reduction activating transcription factor 6-mediated endoplasmic reticulum stress demonstrated treatment. Notably, counteracted -gal-induced depletion nuclear erythroid 2-related 2 level. Moreover, anti-senescence via ability restore balance redox circuit. modulation phosphatidylinositol-3-kinase/protein kinase B/p53 pathway kappa B level, key regulator senescence-associated secretory phenotype mediators release, also elucidated. Altogether, these findings insinuate benefits management. Graphic abstract

Language: Английский

---

Protein Quality Control Systems and ER Stress as Key Players in SARS-CoV-2-Induced Neurodegeneration

Cells, Journal Year: 2024, Volume and Issue: 13(2), P. 123 - 123

Published: Jan. 9, 2024

The COVID-19 pandemic has brought to the forefront intricate relationship between SARS-CoV-2 and its impact on neurological complications, including potential links neurodegenerative processes, characterized by a dysfunction of protein quality control systems ER stress. This review article explores role systems, such as Unfolded Protein Response (UPR), Endoplasmic Reticulum-Associated Degradation (ERAD), Ubiquitin–Proteasome System (UPS), autophagy molecular chaperones, in infection. Our hypothesis suggests that produces stress exploits leading disruption proteostasis cannot be solved host cell. culminates cell death may represent link neurodegeneration.

Language: Английский

---

Effects of a Diabetic Microenvironment on Neurodegeneration: Special Focus on Neurological Cells

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(3), P. 284 - 284

Published: March 15, 2024

Diabetes is a chronic metabolic condition associated with high levels of blood glucose which leads to serious damage the heart, kidney, eyes, and nerves. Elevated brain function cognitive abilities. They also lead various neurological neuropsychiatric disorders, including neurodegeneration decline. High neuronal can cause drastic due neurotoxicity. Astrocytes, type glial cell, play vital role in maintaining through neuron–astrocyte coupling. Hyperglycemia progressive decline networks impairment, contributing dysfunction fostering neurodegenerative environment. In this review, we summarize connections, functions, impairments cells diabetic brain. We effects hyperglycemia on functions

Language: Английский

---

The Potential Mechanism and the Role of Antioxidants in Mitigating Oxidative Stress in Alzheimer’s Disease

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(2)

Published: Feb. 18, 2025

Alzheimer’s disease (AD) is the most prevalent cause of dementia and a significant contributor to health issues mortality among older individuals. This condition involves progressive deterioration in cognitive function onset dementia. Recent advancements suggest that development AD more intricate than its underlying brain abnormalities alone. In addition, disease, metabolic syndrome, oxidative stress are all intricately linked one another. Increased concentrations circulating lipids disturbances glucose homeostasis contribute intensification lipid oxidation, leading gradual depletion body’s antioxidant defenses. heightened metabolism adversely impacts cell integrity, resulting neuronal damage. Pathways commonly acknowledged as contributors pathogenesis include alterations synaptic plasticity, disorganization neurons, death. Abnormal some membrane proteins thought creation amyloid (Aβ) oligomers, which extremely hazardous neurotransmission pathways, especially those involving acetylcholine. The interaction between Aβ oligomers these neurotransmitter systems induce cellular dysfunction, an imbalance signaling, and, ultimately, manifestation neurological symptoms. Antioxidants have impact on human since they may improve aging process by combating free radicals. Neurodegenerative diseases currently incurable; however, be effectively managed. An appealing alternative utilization natural antioxidants, such polyphenols, through diet or dietary supplements, offer numerous advantages. Within this framework, we extensively examined importance advancement well potential influence antioxidants mitigating effects.

Language: Английский

---

Angiotensin‐converting enzymes as druggable features of psychiatric and neurodegenerative disorders

Journal of Neurochemistry, Journal Year: 2023, Volume and Issue: 166(2), P. 138 - 155

Published: March 13, 2023

Abstract The renin‐angiotensin system (RAS) plays essential roles in maintaining peripheral cardiovascular homeostasis, with its potential the brain only being recognized more recently. Angiotensin‐I‐converting enzyme (ACE) is main component of RAS, and it has been implicated various disorders brain. ACE other RAS components, including related ACE2, angiotensin peptides their respective receptors, can participate pathological state, as well to contribute neuroprotection and/or complement existing treatments for psychiatric illness. In this narrative review, we aimed identify studies describing functions ACEs association disorders. These include neurodegenerative such Parkinson's Alzheimer's diseases, illnesses schizophrenia, bipolar disorder, depression. We also discuss possible a functional polymorphism gene these diseases relevance neuroprotective anti‐inflammatory properties inhibitors (ACEis) receptor blockers (ARBs). Based on this, conclude that there significant value inclusion ACEis ARBs novel integrated approach treatment brain, particularly image

Language: Английский

---

The enzymes of the oxidative phase of the pentose phosphate pathway as targets of reactive species: consequences for NADPH production

Biochemical Society Transactions, Journal Year: 2023, Volume and Issue: 51(6), P. 2173 - 2187

Published: Nov. 16, 2023

The pentose phosphate pathway (PPP) is a key metabolic pathway. oxidative phase of this process involves three reactions catalyzed by glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconolactonase (6PGL) and 6-phosphogluconate (6PGDH) enzymes. first third steps (catalyzed G6PDH 6PGDH, respectively) are responsible for generating reduced nicotinamide adenine dinucleotide (NAPDH), cofactor maintaining the reducing power cells detoxification both endogenous exogenous oxidants electrophiles. Despite importance these enzymes, little attention has been paid to fact that proteins targets oxidants. In response stimuli pathways modulated, with PPP often up-regulated in order enhance or maintain reductive capacity cells. Under such circumstances, oxidation inactivation enzymes could be detrimental. Damage may result downward spiral, as depending on extent sites modification, alterations loss enzymatic activity therefore increased damage due NADPH depletion. recent years, it become evident have different susceptibilities exposure review, we discuss existing knowledge role play metabolism cells, their susceptibility special emphasis production. Perspectives achieving better understanding molecular basis within cellular environments given.

Language: Английский

---