Oxidative Stress in Age-Related Neurodegenerative Diseases: An Overview of Recent Tools and Findings

Antioxidants, Год журнала: 2023, Номер 12(1), С. 131 - 131

Опубликована: Янв. 5, 2023

Reactive oxygen species (ROS) have been described to induce a broad range of redox-dependent signaling reactions in physiological conditions. Nevertheless, an excessive accumulation ROS leads oxidative stress, which was traditionally considered as detrimental for cells and organisms, due the damage they cause biomolecules. During ageing, elevated levels result damaged proteins, may exhibit altered enzymatic function or physical properties (e.g., aggregation propensity). Emerging evidence also highlights relationship between stress age-related pathologies, such protein misfolding-based neurodegenerative diseases Parkinson’s (PD), Alzheimer’s (AD) Huntington’s (HD) diseases). In this review we aim introduce role physiology pathology then focus on state-of-the-art techniques available detect quantify oxidized proteins live vivo, providing guide those aiming characterize ageing diseases. Lastly, discuss recently published data neurological disorders.

Язык: Английский

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Alpinetin inhibits neuroinflammation and neuronal apoptosis via targeting the JAK2/STAT3 signaling pathway in spinal cord injury

CNS Neuroscience & Therapeutics, Год журнала: 2023, Номер 29(4), С. 1094 - 1108

Опубликована: Янв. 10, 2023

Abstract Background A growing body of research shows that drug monomers from traditional Chinese herbal medicines have antineuroinflammatory and neuroprotective effects can significantly improve the recovery motor function after spinal cord injury (SCI). Here, we explore role molecular mechanisms Alpinetin on activating microglia‐mediated neuroinflammation neuronal apoptosis SCI. Methods Stimulation microglia with lipopolysaccharide (LPS) to simulate models in vitro, effect release pro‐inflammatory mediators LPS‐induced its mechanism were detected. In addition, a co‐culture system cells was constructed assess apoptosis. Finally, rat used study inflammation, apoptosis, axonal regeneration, Alpinetin. Results inhibits activity JAK2/STAT3 pathway. also reverse activated reactive oxygen species (ROS) production decrease mitochondrial membrane potential (MMP) PC12 cells. vivo inflammatory response improves function. Conclusion be treat neurodegenerative diseases is novel candidate for treatment neuroinflammation.

Язык: Английский

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Misfolding and aggregation in neurodegenerative diseases: protein quality control machinery as potential therapeutic clearance pathways

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Авг. 30, 2024

The primary challenge in today's world of neuroscience is the search for new therapeutic possibilities neurodegenerative disease. Central to these disorders lies among other factors, aberrant folding, aggregation, and accumulation proteins, resulting formation toxic entities that contribute neuronal degeneration. This review concentrates on key proteins such as β-amyloid (Aβ), tau, α-synuclein, elucidating intricate molecular events underlying their misfolding aggregation. We critically evaluate mechanisms governing elimination misfolded shedding light potential strategies. specifically examine pathways endoplasmic reticulum (ER) unfolded protein response (UPR), chaperones, chaperone-mediated autophagy (CMA), intersecting signaling Keap1-Nrf2-ARE, along with connected through p62. Above all, we emphasize significance quality control mechanisms, encompassing interventions targeting regulation post-translational modifications, enhancement chaperones clearance. Additionally, focus current new, multi-target approaches. In conclusion, this systematically consolidates insights into emerging strategies predicated aggregates

Язык: Английский

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Amyloid-β and heart failure in Alzheimer’s disease: the new vistas

Frontiers in Medicine, Год журнала: 2025, Номер 12

Опубликована: Фев. 4, 2025

Alzheimer’s disease (AD) is the most common cause of dementia and represents 75% all types. AD neuropathology due to progressive deposition extracellular amyloid-beta (A β ) peptide intracellular hyperphosphorylated tau protein. The accumulated Aβ forms amyloid plaques, while protein neurofibrillary tangles (NFTs). Both plaques NFTs are hallmarks neuropathology. fundamental mechanism involved in pathogenesis still elusive, although more conceivable theory. Aβ-induced neurodegeneration associated neuroinflammation, oxidative stress, endoplasmic reticulum stress (ER), mitochondrial dysfunction contribute development cognitive impairment dementia. Of note, not only originated from brain but also produced peripherally and, via blood–brain barrier (BBB), can accumulate result AD. It has been shown that cardiometabolic conditions such as obesity, type 2 diabetes (T2D), heart failure (HF) regarded possible risk factors for other types dementia, vascular HF-induced chronic cerebral hypoperfusion, inflammation induce progression Interestingly, a systemic causes which turn affects peripheral organs, including heart. through deranged BBB be transported into circulation heart, leading HF. These findings suggest close relationship between However, exact AD-induced HF fully elucidated. Therefore, this review aims discuss link regarding potential role

Язык: Английский

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Bridging gap in the treatment of Alzheimer’s disease via postbiotics: Current practices and future prospects

Ageing Research Reviews, Год журнала: 2025, Номер unknown, С. 102689 - 102689

Опубликована: Фев. 1, 2025

Язык: Английский

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A Triterpenoid Lupeol as an Antioxidant and Anti-Neuroinflammatory Agent: Impacts on Oxidative Stress in Alzheimer’s Disease

Nutrients, Год журнала: 2023, Номер 15(13), С. 3059 - 3059

Опубликована: Июль 7, 2023

Alzheimer’s disease (AD) is the most common neurodegenerative illustrated by neuronal dysfunctions, leading to memory weaknesses and personality changes mostly in aged population worldwide. The exact cause of AD unclear, but numerous studies have addressed involvement oxidative stress (OS), induced reactive oxygen species (ROS), be one causes developing AD. OS dysregulates cellular homeostasis, causing abnormal protein lipid metabolism. Nutrition plays a pivotal role modulating antioxidant system decreases ROS level, thus playing an important therapeutic diseases, especially Hence, medicinal herbs their extracts received global attention as commercial source antioxidants Lupeol. Lupeol pentacyclic triterpenoid has many biological functions. It available fruits, vegetables, plants. shown effective anti-inflammatory properties, higher blood–brain barrier permeability. Also, binding inhibitory potentials been investigated proved against certain receptor proteins enzymes computational molecular docking approaches. Therefore, AD-related research gained interest investigating effects However, despite its beneficial AD, there still lack we compiled this analysis all preclinical that looked at agent for

Язык: Английский

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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, Год журнала: 2023, Номер 31(5), С. 2653 - 2673

Опубликована: Июль 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

Язык: Английский

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G-quadruplexes and associated proteins in aging and Alzheimer’s disease

Frontiers in Aging, Год журнала: 2023, Номер 4

Опубликована: Июнь 1, 2023

Aging is a prominent risk factor for many neurodegenerative disorders, such as Alzheimer’s disease (AD). characterized by progressive cognitive decline, memory loss, and neuropsychiatric behavioral symptoms, accounting most of the reported dementia cases. This now becoming major challenge burden on modern society, especially with aging population. Over last few decades, significant understanding pathophysiology AD has been gained studying amyloid deposition, hyperphosphorylated tau, synaptic dysfunction, oxidative stress, calcium dysregulation, neuroinflammation. review focuses role non-canonical secondary structures DNA/RNA G-quadruplexes (G4s, G4-DNA, G4-RNA), G4-binding proteins (G4BPs), helicases, their roles in AD. Being critically important cellular function, G4s are involved regulation DNA RNA processes, replication, transcription, translation, localization, degradation. Recent studies have also highlighted G4-DNA’s inducing double-strand breaks that cause genomic instability G4-RNA’s participation regulating stress granule formation. emphasizes significance processes how homeostatic imbalance may contribute to

Язык: Английский

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Photobiomodulation in Alzheimer’s Disease—A Complementary Method to State-of-the-Art Pharmaceutical Formulations and Nanomedicine?

Pharmaceutics, Год журнала: 2023, Номер 15(3), С. 916 - 916

Опубликована: Март 11, 2023

Alzheimer’s disease (AD), as a neurodegenerative disorder, usually develops slowly but gradually worsens. It accounts for approximately 70% of dementia cases worldwide, and is recognized by WHO public health priority. Being multifactorial disease, the origins AD are not satisfactorily understood. Despite huge medical expenditures attempts to discover new pharmaceuticals or nanomedicines in recent years, there no cure many successful treatments available. The current review supports introspection on latest scientific results from specialized literature regarding molecular cellular mechanisms brain photobiomodulation, complementary method with implications AD. State-of-the-art pharmaceutical formulations, development nanoscale materials, bionanoformulations applications perspectives highlighted. Another goal this was speed transition completely paradigms multi-target management AD, facilitate remodeling through therapeutic models high-tech light lasers integrative nanomedicine future. In conclusion, insights interdisciplinary approach, including photobiomodulation (PBM) applied human clinical trials, combined drug delivery systems easily overcome protective barriers, could open avenues rejuvenate our central nervous system, most fascinating complex organ. Picosecond transcranial laser stimulation be successfully used cross blood-brain barrier together nanotechnologies, therapy. Original, smart targeted multifunctional solutions nanodrugs may soon developed treat

Язык: Английский

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Cryo-EM structures of lipidic fibrils of amyloid-β (1-40)

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 13, 2024

Abstract Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative characterized by the extracellular deposition of amyloid plaques. Investigation into composition these plaques revealed high amount amyloid-β (Aβ) fibrils concentration lipids, suggesting that fibril-lipid interactions may also be relevant for pathogenesis AD. Therefore, we grew Aβ40 in presence lipid vesicles determined their structure cryo-electron microscopy (cryo-EM) to resolution. The fold major polymorph similar brain-seeded reported previously. majority lipids are bound fibrils, as show cryo-EM NMR spectroscopy. This apparent extraction from observed here vitro provides structural insights potentially disease-relevant interactions.

Язык: Английский

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