Modulation of Biological Membranes Using Small-Molecule Compounds to Counter Toxicity Caused by Amyloidogenic Proteins DOI Creative Commons

Raina Marie Seychell,

Adam El Saghir,

Neville Vassallo

и другие.

Membranes, Год журнала: 2024, Номер 14(11), С. 231 - 231

Опубликована: Ноя. 6, 2024

The transition of peptides or proteins along a misfolding continuum from soluble functional states to pathological aggregates, ultimately deposit as amyloid fibrils, is process that underlies an expanding group human diseases-collectively known protein-misfolding disorders (PMDs). These include common and debilitating conditions, such Alzheimer's disease, Parkinson's type-2 diabetes. Compelling evidence has emerged the complex interplay between misfolded biological membranes key determinant pathogenic mechanisms by which harmful entities are formed exert their cytotoxicity. Most efforts thus far develop disease-modifying treatments for PMDs have largely focused on anti-aggregation strategies: neutralise, prevent formation of, toxic species. Herein, we review critical role phospholipid membrane in mediating enabling pathogenicity. We consequently propose development small molecules, potential uniquely modify physicochemical properties make it more resilient against damage proteins, could provide novel therapeutic approach PMDs. By way example, natural compounds shown intercalate into lipid bilayers inhibit amyloid-lipid interactions, aminosterols, squalamine trodusquamine, cholesterol, ubiquinone, select polyphenols, discussed. Such strategy would counter wide range biomolecules implicit numerous pathologies.

Язык: Английский

Ferroptosis in Cancer Therapy: Mechanisms, Small Molecule Inducers, and Novel Approaches DOI Creative Commons

YiLin Luo,

Xin Yue Bai,

L.J. Zhang

и другие.

Drug Design Development and Therapy, Год журнала: 2024, Номер Volume 18, С. 2485 - 2529

Опубликована: Июнь 1, 2024

Abstract: Ferroptosis, a unique form of programmed cell death, is initiated by an excess iron accumulation and lipid peroxidation-induced damage. There growing body evidence indicating that ferroptosis plays critical role in the advancement tumors. The increased metabolic activity higher levels tumor cells make them particularly vulnerable to ferroptosis. As result, targeted induction becoming increasingly promising approach for cancer treatment. This review offers overview regulatory mechanisms ferroptosis, delves into mechanism action traditional small molecule inducers their effects on various In addition, latest progress inducing using new means such as proteolysis-targeting chimeras (PROTACs), photodynamic therapy (PDT), sonodynamic (SDT) nanomaterials summarized. Finally, this discusses challenges opportunities development ferroptosis-inducing agents, focusing discovering targets, improving selectivity, reducing toxic side effects. Keywords: inducers, molecules, PROTACs, PDT, SDT,

Язык: Английский

Процитировано

8
Curcumin: A Golden Approach to Healthy Aging: A Systematic Review of the Evidence DOI Open Access

Yandra Cervelim Nunes,

Nathalia. M. Mendes,

Enzo Pereira de Lima

и другие.

Опубликована: Июль 12, 2024

Aging-related disorders pose significant challenges due to their complex interplay of physiological and metabolic factors, including inflammation, oxidative stress, mitochondrial dysfunction. Curcumin, a natural compound with potent antioxidant anti-inflammatory properties, has emerged as promising candidate for mitigating these age-related processes. However, gaps in understanding the precise mechanisms curcumin's effects optimal dosages different conditions necessitate further investigation. This systematic review synthesizes current evidence on potential addressing disorders, emphasizing its impact cognitive function, neurodegeneration, muscle health older adults. By evaluating safety, efficacy, action curcumin supplementation, this aims provide insights into therapeutic promoting healthy aging. A search across three databases using specific keywords yielded 2,256 documents, leading selection 15 clinical trials synthesis. Here we highlight multifaceted agent combating disorders. The findings suggest that could offer effective approach enhancing quality life aging individuals. Further research well-designed are essential validate optimize use personalized medicine approaches conditions.

Язык: Английский

Процитировано

8
Curcumin: A Golden Approach to Healthy Aging: A Systematic Review of the Evidence DOI Open Access

Yandra Cervelim Nunes,

Nathalia. M. Mendes,

Enzo Pereira de Lima

и другие.

Nutrients, Год журнала: 2024, Номер 16(16), С. 2721 - 2721

Опубликована: Авг. 15, 2024

Aging-related disorders pose significant challenges due to their complex interplay of physiological and metabolic factors, including inflammation, oxidative stress, mitochondrial dysfunction. Curcumin, a natural compound with potent antioxidant anti-inflammatory properties, has emerged as promising candidate for mitigating these age-related processes. However, gaps in understanding the precise mechanisms curcumin’s effects optimal dosages different conditions necessitate further investigation. This systematic review synthesizes current evidence on potential addressing disorders, emphasizing its impact cognitive function, neurodegeneration, muscle health older adults. By evaluating safety, efficacy, action curcumin supplementation, this aims provide insights into therapeutic promoting healthy aging. A search across three databases using specific keywords yielded 2256 documents, leading selection 15 clinical trials synthesis. Here, we highlight multifaceted agent combating disorders. The findings suggest that could offer effective approach enhancing quality life aging individuals. Further research well-designed are essential validate optimize use personalized medicine approaches conditions.

Язык: Английский

Процитировано

8
Antioxidant and anti-Alzheimer's disease activities of 1,8-cineole and its cyclodextrin inclusion complex DOI Open Access
Xin Tan, Rui Xu,

А. А. Ли

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 175, С. 116784 - 116784

Опубликована: Май 22, 2024

1,8-Cineole is a bicyclic monoterpene widely distributed in the essential oils of various medicinal plants, and it exhibits significant anti-inflammatory antioxidant activities. We aimed to investigate therapeutic effect 1,8-cineole on anti-Alzheimer's disease by using transgenic Caenorhabditis elegans models. Our studies demonstrated that significantly relieved Aβ1–42-induced paralysis exhibited remarkable anti-Aβ1–42 aggregation activities nematodes CL4176, CL2006 CL2355. developed 1,8-cineole/cyclodextrin inclusion complex, displaying enhanced anti-paralysis, anti-Aβ compared 1,8-cineole. In addition, we found treatment activated SKN-1/Nrf-2 pathway induced autophagy nematodes. results 1,8-cineole, which provide potential approach for Alzheimer's disease.

Язык: Английский

Процитировано

6
The Interplay of Protein Aggregation, Genetics, and Oxidative Stress in Alzheimer’s Disease: Role for Natural Antioxidants and Immunotherapeutics DOI Creative Commons
Ali Jawad, Kyonghwan Choe, Jun Sung Park

и другие.

Antioxidants, Год журнала: 2024, Номер 13(7), С. 862 - 862

Опубликована: Июль 18, 2024

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that comprises amyloid-beta protein (Aβ) as main component of neuritic plaques. Its deposition considered trigger for AD pathogenesis, progression, and the clinical symptoms cognitive impairment. Some distinct pathological features include phosphorylation tau protein, oxidative stress, mitochondrial dysfunction. These consequences tend to produce reactive oxygen species (ROS), resulting in dysregulation various signaling pathways neuroinflammation neurodegeneration. The relationship between Aβ cascade stress pathogenesis like “chicken egg” story, with etiology regarding these two factors remaining question “which comes first.” However, this review, we have tried our best clarify interconnection mechanisms show precise cause-and-effect relationship. Based on above hallmarks AD, several therapeutic strategies using natural antioxidants, monoclonal antibodies, vaccines are employed anti-Aβ therapy decrease ROS, burden, chronic neuroinflammation, synaptic failure. antioxidants immunotherapeutics demonstrated significant neuroprotective effects symptomatic relief vitro vivo models, well trials AD. none them received final approval enter drug market mitigating In extensively elaborate pitfalls, assurances, important crosstalk concerning current therapy. Additionally, discuss future development more Aβ-targeted approaches optimization treatment mitigation.

Язык: Английский

Процитировано

6
Infectious viruses and neurodegenerative diseases: The mitochondrial defect hypothesis DOI

Tianshi Jiang,

Kaili Zhu,

Gloria Kang

и другие.

Reviews in Medical Virology, Год журнала: 2024, Номер 34(4)

Опубликована: Июнь 21, 2024

Abstract Global attention is riveted on neurodegenerative diseases due to their unresolved aetiologies and lack of efficacious therapies. Two key factors implicated include mitochondrial impairment microglial ageing. Several viral infections, including Herpes simplex virus‐1 (HSV‐1), human immunodeficiency virus (HIV) Epstein‐Barr virus, are linked heightened risk these disorders. Surprisingly, numerous studies indicate viruses induce aforementioned precipitating events. Hepatitis C Virus, HIV, respiratory syncytial HSV‐1, Japanese Encephalitis Zika Enterovirus 71 specifically impact function, leading malfunction. These vital organelles govern various cell activities and, under specific circumstances, trigger This article explores the role infections in elucidating pathogenesis ailments. Various instigate ageing via destruction, causing senescent microglia exhibit activated behaviour, thereby inducing neuroinflammation contributing neurodegeneration.

Язык: Английский

Процитировано

4
Low-intensity pulsed ultrasound enhances delivery of 30 nm Q10 for improving mental and memory disorder in APP/PS1 mice DOI
Qi Luo, Xuanjie Ye, Jinan Xu

и другие.

Drug Delivery and Translational Research, Год журнала: 2025, Номер unknown

Опубликована: Фев. 24, 2025

Язык: Английский

Процитировано

0
Exploring Alzheimer's Disease Treatment: Established Therapies and Novel Strategies for Future Care DOI
Urvashi Soni, Kuldeep Singh, Divya Jain

и другие.

European Journal of Pharmacology, Год журнала: 2025, Номер unknown, С. 177520 - 177520

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Acid-assisted polysaccharides extracted from Asparagus cochinchinensis protect against Alzheimer’s disease by regulating the microbiota-gut-brain axis DOI Creative Commons
Ruixue Li, Hui Wang, Qinjian Wang

и другие.

Frontiers in Nutrition, Год журнала: 2024, Номер 11

Опубликована: Дек. 18, 2024

In this study, an acid-assisted extraction strategy was used to extract a novel polysaccharide (ACP) from Asparagus cochinchinensis, after which purified and subjected extensive characterization. ACP determined have average molecular weight of 15,580 Da in structural characterization studies, it found primarily consist glucose, galactose, L-fucose, fructose at 82.14:12.23:2.61:2.49 ratio. Trace amounts xylose, arabinose, rhamnose were also detected preparations 0.48:0.04:0.02 GC–MS analyses identified eight different sugar linkages within ACP, including Glc p -(1→, →2)-Glc →6)-Glc →4)-Glc →3, 4)-Glc →2,4) -Gal →4,6)-Gal →3,4,6)-Gal -(1 → present 23.70:1.30:3.55:50.77:6.91:1.10:11.50:1.18 molar percent ratios. One-dimensional NMR, two-dimensional methylation ultimately revealed that the is mainly composed →4)- β -D-Glc small amount→4,6)- α -D-Gal →3,4)- so on. Branched chain α-D-Glc 4)- connected residues 4)-β-D-Glc O-4 position or O-3 position. treatment SAMP8 mice associated with reductions oxidative stress brain pathology together enhanced cognitive function. treated presented increases Bacteroidota abundance reduced Firmicutes, Patescibacteria, Actinobacteriota, Campilobacterota abundance. Thus, can prevent Alzheimer’s disease by modulating microbe-gut-brain axis.

Язык: Английский

Процитировано

1
The Role of Antioxidants in the Treatment of Alzheimer’s Disease DOI
Veysel Tahiroğlu

Опубликована: Июнь 7, 2024

Alzheimer disease is a chronic, progressive neurodegenerative characterized by cognitive impairment. It the most common form of dementia in elderly population and its impact increasing worldwide. More than 47 million people worldwide are thought to be affected disease. Age leading risk factor, research has shown that over 60 more likely develop Alzheimer. Oxidation events constantly occur living metabolism, reactive oxygen substances taken from outside accelerate these oxidation events. Cell damage may as result increase free radicals body potential cause serious health problems. In order prevent disease, which associated with radical levels, oxidant must balanced antioxidants. possible get rid negative effects diet sufficient antioxidant intake. Therefore, antioxidants an important defense mechanism reduce oxidant-related diseases for better quality longer life. addition, metals such iron, copper zinc enzymes brain function metabolic processes myelination neurotransmitter synthesis. However, it known accumulation disruption homeostasis also pose pathology. Considering all situations, role treatment examined this section.

Язык: Английский

Процитировано

0