Cysteine in the R3 Tau Peptide Modulates Hemin Binding and Reactivity DOI
Chiara Bacchella,

Teresa Benedetta Guerriere,

Enrico Monzani

et al.

Inorganic Chemistry, Journal Year: 2024, Volume and Issue: 63(26), P. 11986 - 12002

Published: June 19, 2024

Tau is a neuronal protein involved in axonal stabilization; however under pathological conditions, it triggers the deposition of insoluble neurofibrillary tangles, which are one biomarkers for Alzheimer's disease. The factors that might influence fibrillation process i) two cysteine residues pseudorepetitive regions, called R2 and R3, can modulate protein–protein interaction via disulfide cross-linking; ii) an increase reactive oxygen species affecting post-translational modification tau; iii) cytotoxic levels metals, especially ferric-heme (hemin), hemolytic processes. Herein, we investigated how cysteine-containing R3 peptide (R3C) its Cys→Ala mutant (R3A) interact with hemin their binding affects oxidative damage protein. calculated constants remarkably higher hemin-R3C complex (LogK1 = 5.90; LogK2 5.80) respect to R3A 4.44; < 2), although NMR CD investigations excluded direct as iron axial ligand. Both peptides peroxidase-like activity toward catecholamines phenols, double catalytic efficiency detected systems. Moreover, presence significantly alters susceptibility modifications, easily resulting dopamination formation cross-linked S–S derivatives.

Language: Английский

Signal pathways in the treatment of Alzheimer’s disease with traditional Chinese medicine DOI Open Access

Min-Rui Ding,

Yan-Jie Qu,

Bing Hu

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 152, P. 113208 - 113208

Published: May 31, 2022

This study aimed to reveal the classical signal pathways and important potential targets of traditional Chinese medicine (TCM) for treating Alzheimer's disease (AD), provide support further investigation on TCM its active ingredients.Literature survey was conducted using PubMed, Web Science, Google Scholar, CNKI, other databases, with "Alzheimer's disease," "traditional medicine," "medicinal herb," "Chinese "natural plant" as primary keywords.TCM could modulate related AD pathological progression, including NF-κB, Nrf2, JAK/STAT, ubiquitin-proteasome pathway, autophagy-lysosome pathway-related AMPK/mTOR, GSK-3/mTOR, PI3K/Akt/mTOR, well SIRT1 PPARα pathway. It regulate crosstalk between through a multitarget, thus maintaining chronic inflammatory interaction balance, inhibiting oxidative stress damage, regulating system function, modulating autophagy, eventually improving cognitive impairment in patients AD.TCM be multilevel, multitargeted, multifaceted prevent treat AD. In-depth research prevention treatment new ideas exploring pathogenesis developing anti-AD drugs.

Language: Английский

Citations

85
Oxidative stress, the blood–brain barrier and neurodegenerative diseases: The critical beneficial role of dietary antioxidants DOI Creative Commons
Feng Jin,

Youle Zheng,

Mingyue Guo

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 13(10), P. 3988 - 4024

Published: July 16, 2023

In recent years, growing awareness of the role oxidative stress in brain health has prompted antioxidants, especially dietary to receive attention as possible treatments strategies for patients with neurodegenerative diseases (NDs). The most widely studied antioxidants include active substances such vitamins, carotenoids, flavonoids and polyphenols. Dietary are found usually consumed foods fresh fruits, vegetables, nuts oils gaining popularity due recently their potential preventive protective agents against NDs, well abundant natural sources, generally non-toxic nature, ease long-term consumption. This review article examines development explores ‘two-sidedness’ blood–brain barrier (BBB) a nervous system an impeding use drug medicinal products and/or supplements prevention therapy reviews BBB permeability common suplements efficacy treatment NDs. Finally, current challenges future directions NDs using discussed, useful information on is provided.

Language: Английский

Citations

67
NRF2 Deficiency Promotes Ferroptosis of Astrocytes Mediated by Oxidative Stress in Alzheimer’s Disease DOI
Zhi Tang,

Zhuyi Chen,

Min Guo

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(10), P. 7517 - 7533

Published: Feb. 24, 2024

Language: Английский

Citations

24
Integrative metabolomics science in Alzheimer’s disease: Relevance and future perspectives DOI
Simone Lista, Raúl González‐Domínguez, Susana López‐Ortiz

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 89, P. 101987 - 101987

Published: June 19, 2023

Language: Английский

Citations

34
The Dual Role of Amyloid Beta-Peptide in Oxidative Stress and Inflammation: Unveiling Their Connections in Alzheimer’s Disease Etiopathology DOI Creative Commons
Hugo Fanlo-Ucar, Pol Picón-Pagès, Víctor Herrera-Fernández

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(10), P. 1208 - 1208

Published: Oct. 8, 2024

Alzheimer's disease (AD) is a progressive neurodegenerative disease, and it currently the seventh leading cause of death worldwide. It characterized by extracellular aggregation amyloid β-peptide (Aβ) into oligomers fibrils that synaptotoxicity neuronal death. Aβ exhibits dual role in promoting oxidative stress inflammation. This review aims to unravel intricate connection between these processes their contribution AD progression. The delves AD, focusing on involvement metals, mitochondrial dysfunction, biomolecule oxidation. distinct yet overlapping concept nitro-oxidative also discussed, detailing roles nitric oxide, perturbations, cumulative impact production neurotoxicity. Inflammation examined through astroglia microglia function, elucidating response within brain. blood-brain barrier oligodendrocytes are considered context pathophysiology. We current diagnostic methodologies emerging therapeutic strategies aimed at mitigating inflammation, thereby offering potential treatments for halting or slowing comprehensive synthesis underscores pivotal bridging advancing our understanding informing future research treatment paradigms.

Language: Английский

Citations

10
Natural antioxidants that act against Alzheimer’s disease through modulation of the NRF2 pathway: a focus on their molecular mechanisms of action DOI Creative Commons

Grammatiki Alexandra Sidiropoulou,

Athanasios Metaxas, Malamati Kourti

et al.

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

Published: July 3, 2023

Characterized by a complex pathophysiology that includes the intraneuronal formation of neurofibrillary tangles and extracellular deposition β-amyloid plaques, Alzheimer’s disease (AD) is terminal neurodegenerative causes dementia in older adults. Oxidative stress brain considered as one contributing factors to pathogenesis AD, thus, antioxidants have attracted much interest potential therapeutic agents against disorder. Natural are typically characterized low acute chronic toxicity, which facilitates their application. One important molecular target for beneficial effects natural nuclear factor erythroid-derived 2-related 2 (NFE2L2/NRF2). NRF2 key transcription orchestrates cellular antioxidant response through regulating expression oxidative stress-related genes harboring element (ARE) promoters. Indeed, case excessive damage, migrates nucleus binds ARE, activating protector genes. There increasing evidence implicated AD pathology dysfunction altered localization, renders it AD. Thus, this review summarizes most recent (2018-2023) advances on NRF2-modulating activity observed vitro animal models. This information will help elucidate mechanisms governing such phytochemicals highlight common diseases,

Language: Английский

Citations

17
Using Redox Proteomics to Gain New Insights into Neurodegenerative Disease and Protein Modification DOI Creative Commons
Paula Cadenas-Garrido,

Ailén Schonvandt-Alarcos,

Lourdes Herrera‐Quintana

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(1), P. 127 - 127

Published: Jan. 20, 2024

Antioxidant defenses in biological systems ensure redox homeostasis, regulating baseline levels of reactive oxygen and nitrogen species (ROS RNS). Oxidative stress (OS), characterized by a lack antioxidant or an elevation ROS RNS, may cause modification biomolecules, being primarily absorbed proteins. As result both genome environment interactions, proteomics provides complete information about cell’s proteome, which changes continuously. Besides measuring protein expression levels, can also be used to identify modifications, localizations, the effects added agents, interactions between Several oxidative processes are frequently modify proteins post-translationally, including carbonylation, oxidation amino acid side chains, glycation, lipid peroxidation, produces highly alkenals. Reactive alkenals, such as 4-hydroxy-2-nonenal, cysteine (Cys), lysine (Lys), histidine (His) residues Michael addition, tyrosine (Tyr) nitrated Cys nitrosylated addition. nitrosative have been implicated many neurodegenerative diseases damage brain, especially vulnerable due large consumption dioxygen. Therefore, current methods applied for detection, identification, quantification great interest. This review describes main modifications classified chemical reactions. Finally, we discuss importance health describe analytical proteomics.

Language: Английский

Citations

8
Oxidative stress and aging: synergies for age related diseases DOI
Daniela F. Santos, Sónia Simão, Clévio Nóbrega

et al.

FEBS Letters, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 7, 2024

Aging is characterized by a progressive decline in physiological function and underlies several disabilities, including the increased sensitivity of cells tissues to undergo pathological oxidative stress. In recent years, efforts have been made better understand relationship between age stress further develop therapeutic strategies minimize impact both events on age-related diseases. this work, we review oxidant antioxidant systems during aging disease development discuss crosstalk other processes, with focus studies conducted elderly populations.

Language: Английский

Citations

7
Gut microbiota may be involved in Alzheimer’s disease pathology by dysregulating pyrimidine metabolism in APP/PS1 mice DOI Creative Commons

Min Feng,

Tianshu Hou,

Mingze Zhou

et al.

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

Published: Aug. 3, 2022

Alzheimer's disease (AD) is the most common form of dementia worldwide. The biological mechanisms underlying pathogenesis AD aren't completely clear. Studies have shown that gut microbiota could be associated with pathogenesis; however, pathways involved still need to investigated.To explore possible involvement in through metabolites and identify new biomarkers.Seven-month-old APP/PS1 mice were used as models. Morris water maze test was examine learning memory ability. 16S rRNA gene sequencing widely targeted metabolomics composition fecal metabolic profile, respectively, followed by a combined analysis microbiomics metabolomics.Impaired abilities observed mice. Statistically significant changes detected, including reduction β-diversity, higher ratio Firmicutes/Bacteroidota, multiple differential bacteria. metabolism also 40 perturbations pyrimidine metabolism. Approximately 40% markedly microbiota, top two bacteria Bacillus firmus Rikenella. Deoxycytidine, which causes pathway, significantly correlated Clostridium sp. Culture-27.Gut may pathological processes cognitive impairment dysregulating B. firmus, Rikenella, Culture-27, deoxyuridine important markers for AD. Our findings provide insights into host-microbe crosstalk pathology contribute discovery diagnostic therapeutic targets

Language: Английский

Citations

23
Therapeutic Potential of Targeting Mitochondria for Alzheimer’s Disease Treatment DOI Open Access
Anna Atlante, Giuseppina Amadoro, Valentina Latina

et al.

Journal of Clinical Medicine, Journal Year: 2022, Volume and Issue: 11(22), P. 6742 - 6742

Published: Nov. 14, 2022

Alzheimer's disease (AD), a chronic and progressive neurodegenerative disease, is characterized by memory cognitive impairment the accumulation in brain of abnormal proteins, more precisely beta-amyloid (β-amyloid or Aβ) Tau proteins. Studies aimed at researching pharmacological treatments against AD have focused on molecules capable, one way another, preventing/eliminating accumulations aforementioned Unfortunately, than 100 years after discovery there still no effective therapy modifying biology behind nipping bud. This state affairs has made neuroscientists suspicious, so much that for several idea gained ground not direct neuropathological consequence taking place downstream deposition two toxic but rather multifactorial including mitochondrial dysfunction as an early event pathogenesis AD, occurring even before clinical symptoms. reason why search agents capable normalizing functioning these subcellular organelles vital importance nerve cells certainly to be considered promising approach design neuroprotective drugs preserving this organelle arrest delay progression disease. Here, our intent provide updated overview alterations related disorder therapeutic strategies (both natural synthetic) targeting dysfunction.

Language: Английский

Citations

23