Natural Carotenoids as Neuroprotective Agents for Alzheimer’s Disease: An Evidence-Based Comprehensive Review DOI
Zahra Batool, Jie‐Hua Chen, Yao Gao

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2022, Volume and Issue: 70(50), P. 15631 - 15646

Published: Dec. 8, 2022

Alzheimer's disease (AD) is a neurodegenerative disorder of an ever-increasing aging population with various pathological features such as β-amyloid (Aβ) aggregation, oxidative stress, impaired cholinergic system, and neuroinflammation. Several therapeutic drugs have been introduced to slow the progression AD by targeting above-mentioned pathways. In addition, emerging evidence suggests that naturally occurring compounds potential serve adjuvant therapies alleviate symptoms. Carotenoids, group natural pigments antioxidative anti-inflammatory properties, are proposed be implicated in neuroprotection. To obtain comprehensive picture effect carotenoids on prevention development, we critically reviewed discussed recent from silico, vitro, vivo, human studies databases including PubMed, Web Science, Google Scholar, Cochrane (CENTRAL). After analyzing existing evidence, found high-quality randomized controlled trials (RCTs) lacking explore neuroprotective role pathogenesis symptoms, especially solid preclinical astaxanthin, fucoxanthin, macular carotenoids, crocin, order develop effective preventive dietary supplements for patients ameliorate This review points out directions future advance knowledge this field.

Language: Английский

Cardiometabolic risk factors and neurodegeneration: a review of the mechanisms underlying diabetes, obesity and hypertension in Alzheimer’s disease DOI Creative Commons

Vijay Patel,

Paul Edison

Journal of Neurology Neurosurgery & Psychiatry, Journal Year: 2024, Volume and Issue: 95(6), P. 581 - 589

Published: Jan. 30, 2024

A growing body of evidence suggests that cardiometabolic risk factors play a significant role in Alzheimer’s disease (AD). Diabetes, obesity and hypertension are highly prevalent can accelerate neurodegeneration perpetuate the burden AD. Insulin resistance enzymes including insulin degrading implicated AD where breakdown is prioritised over amyloid-β. Leptin inflammation demonstrated by higher plasma central nervous system levels interleukin-6 (IL-6), IL-1β tumour necrosis factor-α, mechanisms connecting diabetes with has been shown to ameliorate pathology enhance long-term potentiation hippocampal-dependent cognitive function. The renin-aldosterone angiotensin system, involved hypertension, associated neurotoxic reactive oxygen species, binds specific angiotensin-1 receptors hippocampus cerebral cortex. This review aims consolidate behind putative processes stimulated obesity, which leads increased risk. We focus on how novel knowledge be applied clinically facilitate recognition efficacious treatment strategies for

Language: Английский

Citations

26
The GLP-1 Agonist Semaglutide Ameliorates Cognitive Regression in P301S Tauopathy Mice Model via Autophagy/ACE2/SIRT1/FOXO1-Mediated Microglia Polarization DOI
Norhan N. Elbadawy, Muhammed A. Saad, Sara Elfarrash

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177305 - 177305

Published: Jan. 1, 2025

Language: Английский

Citations

2
Re-Routing Drugs to Blood Brain Barrier: A Comprehensive Analysis of Machine Learning Approaches With Fingerprint Amalgamation and Data Balancing DOI Creative Commons
Mohammed Yusuf Ansari,

Vaisali Chandrasekar,

Ajay Vikram Singh

et al.

IEEE Access, Journal Year: 2022, Volume and Issue: 11, P. 9890 - 9906

Published: Dec. 29, 2022

Computational drug repurposing is an efficient method to utilize existing knowledge for understanding and predicting their effect on neurological diseases. The ability of a molecule cross the blood-brain barrier primary criteria effective therapy. Thus, accurate predictions by employing Machine learning models can effectively identify candidates that could be repurposed conditions. This study comprehensively analyzes performance well-known machine two different datasets overcome dataset-related biases. We found random forest extratrees (i.e., tree-based ensembled models) have highest accuracy with mol2vec fingerprint BBB permeability prediction, attaining AUC_ROC 0.9453 0.9601 B3DB dataset, respectively. Additionally, we analyzed impact data balancing technique SMOTE) improve specificity models. Finally, explored combinations accuracy. By SMOTE combination, SVC attains 0.9511 dataset. used best-performing dataset evaluate drugs intended repurposing. Model validation predicted non-passage most antihypertensive passage CYP17A1 cancer drugs.

Language: Английский

Citations

60
The COVID-19 pandemic and Alzheimer’s disease: mutual risks and mechanisms DOI Creative Commons
Feng Chen, Yan‐Ting Chen, Yongxiang Wang

et al.

Translational Neurodegeneration, Journal Year: 2022, Volume and Issue: 11(1)

Published: Sept. 11, 2022

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a life-threatening disease, especially in elderly individuals and those with comorbidities. The predominant clinical manifestation of COVID-19 dysfunction, while neurological presentations are increasingly being recognized. SARS-CoV-2 invades host cells primarily via attachment the spike protein to angiotensin-converting enzyme (ACE2) receptor expressed on cell membranes. Patients Alzheimer's (AD) more susceptible infection prone outcomes. Recent studies have revealed some common risk factors for AD COVID-19. An understanding association between potential related mechanisms may lead development novel approaches treating both diseases. In present review, we first summarize central nervous system (CNS) then discuss associations shared key AD, focus ACE2 receptor, apolipoprotein E (APOE) genotype, age, neuroinflammation.

Language: Английский

Citations

46
The Renin Angiotensin System as a Therapeutic Target in Traumatic Brain Injury DOI Creative Commons
Sonia Villapol, Zachary C. Janatpour, Kwame Ofori Affram

et al.

Neurotherapeutics, Journal Year: 2023, Volume and Issue: 20(6), P. 1565 - 1591

Published: Sept. 27, 2023

Language: Английский

Citations

21
Intranasal irbesartan reverts cognitive decline and activates the PI3K/AKT pathway in an LPS-induced neuroinflammation mice model DOI Creative Commons
Filipa Gouveia, Carla Fonseca, Ana Silva

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 128, P. 111471 - 111471

Published: Jan. 9, 2024

New strategies are urgently needed to manage and delay the development of Alzheimer's disease (AD). Neuroinflammation is a significant contributor cognitive decline in neurodegenerative diseases, including AD. Angiotensin receptor blockers (ARBs) angiotensin converting enzyme inhibitors (ACEIs) protect hypertensive patients against AD, but cellular molecular mechanisms underlying these effects remain unknown. In light this, protective three ARBs ACEIs neuroinflammation were investigated through comprehensive pharmacologicalin vitro/in vivoscreening.

Language: Английский

Citations

8
Under the umbrella of depression and Alzheimer’s disease physiopathology: Can cannabinoids be a dual-pleiotropic therapy? DOI Creative Commons
Carla Fonseca, Miren Ettcheto, Joana Bicker

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 90, P. 101998 - 101998

Published: July 5, 2023

Depression and Alzheimer´s disease (AD) are two disorders highly prevalent worldwide. affects more than 300 million people worldwide while AD 60% to 80% of the 55 cases dementia. Both diseases affected by aging with high prevalence in elderly share not only main brain areas but also several physiopathological mechanisms. is already ascribed as a risk factor development AD. Despite wide diversity pharmacological treatments currently available clinical practice for depression management, they remain associated slow recovery process treatment-resistant depression. On other hand, treatment essentially based symptomatology relieve. Thus, need new multi-target arises. Herein, we discuss current state-of-art regarding contribution endocannabinoid system (ECS) synaptic transmission processes, synapses plasticity neurogenesis consequently use exogenous cannabinoids on delaying progression Besides well-known imbalance neurotransmitter levels, including serotonin, noradrenaline, dopamine glutamate, recent scientific evidence highlights aberrant spine density, neuroinflammation, dysregulation neurotrophic levels formation amyloid beta (Aβ) peptides, mechanisms compromised The ECS these herein specified well pleiotropic effects phytocannabinoids. At end, it became evident that Cannabinol, Cannabidiol, Cannabigerol, Cannabidivarin Cannabichromene may act novel therapeutic targets, presenting potential pharmacotherapy both diseases.

Language: Английский

Citations

15
Renin–angiotensin system inhibitors positively impact on multiple aging regulatory pathways: Could they be used to protect against human aging? DOI Creative Commons
Elena M. V. de Cavanagh, Felipe Inserra, León Ferder

et al.

Physiological Reports, Journal Year: 2024, Volume and Issue: 12(12)

Published: June 1, 2024

The renin-angiotensin system (RAS)-a classical blood pressure regulator-largely contributes to healthy organ development and function. Besides, RAS activation promotes age-related changes age-associated diseases, which are attenuated/abolished by RAS-blockade in several mammalian species. RAS-blockers also increase rodent lifespan. In previous work, we discussed how downregulates mTOR growth hormone/IGF-1 signaling, stimulates AMPK activity (together with klotho, sirtuin, vitamin D-receptor upregulation), proposed that at least some of RAS-blockade's aging benefits mediated through regulation these intermediaries their signaling mitochondria. Here, included impact on other regulatory pathways, is, TGF-ß, NF-kB, PI3K, MAPK, PKC, Notch, Wnt, all affect No direct evidence is available RAS/RAS-blockade-aging pathway-mitochondria interactions. However, existing results allow conjecture neutralize mitochondrial dysfunction acting the pathways. reviewed led us propose foundation laid for conducting clinical trials aimed testing whether angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB)-even subclinical doses-offer possibility live longer better health. As ACEi ARB low cost well-tolerated anti-hypertension therapies use over 35 years, investigating administration attenuate/prevent effects seems simple implement.

Language: Английский

Citations

6
Acute Myocardial Infarction and Risk of Cognitive Impairment and Dementia: A Review DOI Creative Commons
Elizabeth Thong, Joo Wei Ethan Quek, Jing Hong Loo

et al.

Biology, Journal Year: 2023, Volume and Issue: 12(8), P. 1154 - 1154

Published: Aug. 21, 2023

Cognitive impairment (CI) shares common cardiovascular risk factors with acute myocardial infarction (AMI), and is increasingly prevalent in our ageing population. Whilst AMI associated increased rates of CI, CI remains underreported infrequently identified patients AMI. In this review, we discuss the evidence surrounding its links to dementia including pathophysiology, factors, management interventions. Vascular dysregulation plays a major role atherosclerosis, platelet activation, microinfarcts perivascular inflammation resulting neurovascular unit dysfunction, disordered homeostasis dysfunctional neurohormonal response. This subsequently affects perfusion pressure, enlarged periventricular spaces hippocampal sclerosis. The activation seen coronary artery disease (CAD) can also result amyloid-β protein deposition which Alzheimer’s Dementia. Post-AMI, reduced blood pressure left ventricular ejection fraction cause chronic cerebral hypoperfusion, failure normal circulatory autoregulatory mechanisms. Patients who undergo revascularization (percutaneous intervention or bypass surgery) are at for post-procedure cognitive impairment, though whether related itself underlying debated. Mortality higher AMI, post-AMI more elderly heart failure. Medical (antiplatelet, statin, renin-angiotensin system inhibitors, cardiac rehabilitation) reduce CI; however, beta-blockers may be functional decline existing CI. early identification those present important, as subsequent tailoring strategies potentially improve outcomes well guide prognosis.

Language: Английский

Citations

13
The Role of Furin in the Pathogenesis of COVID-19-Associated Neurological Disorders DOI Creative Commons
Gunel Ayyubova, Sergiy G. Gychka,

Sofia I. Nikolaienko

et al.

Life, Journal Year: 2024, Volume and Issue: 14(2), P. 279 - 279

Published: Feb. 19, 2024

Neurological disorders have been reported in a large number of coronavirus disease 2019 (COVID-19) patients, suggesting that this may long-term adverse neurological consequences. COVID-19 occurs from infection by positive-sense single-stranded RNA virus called severe acute respiratory syndrome 2 (SARS-CoV-2). The membrane fusion protein SARS-CoV-2, the spike protein, binds to its human host receptor, angiotensin-converting enzyme (ACE2), initiate between and cell. SARS-CoV-2 contains furin protease recognition site cleavage enhances infectivity virus. binding ACE2 receptor has shown downregulate ACE2, thereby increasing levels pathogenic angiotensin II (Ang II). cleaves S1 subunit with domain toward S2 transmembrane anchors viral membrane, activity releases into blood circulation. released also downregulates turn level Ang II. Considering particle many molecules, furin-dependent would release free each which can while only affects one molecule. Therefore, dramatically amplify ability produce We hypothesize amplification mechanism possesses, but not per se, is major driving force behind COVID-19-associated disorders.

Language: Английский

Citations

5