White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): Knowledge gaps and opportunities

Alzheimer s & Dementia Translational Research & Clinical Interventions, Journal Year: 2019, Volume and Issue: 5(1), P. 107 - 117

Published: Jan. 1, 2019

Abstract White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs associated with increased likelihood cognitive impairment and dementia (including Alzheimer's disease [AD]). also in cognitively healthy In this collaboration academic, clinical, pharmaceutical industry perspectives, we identify outstanding questions about their relation to cognition, dementia, AD. What molecular cellular changes underlie WMHs? the neuropathological correlates To what extent demyelination inflammation present? Is it helpful subdivide into periventricular subcortical do signify people diagnosed AD? risk factors developing preventive therapeutic strategies target Answering these will improve prevention treatment dementia.

Language: Английский

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COVID-19-associated fungal infections

Nature Microbiology, Journal Year: 2022, Volume and Issue: 7(8), P. 1127 - 1140

Published: Aug. 2, 2022

Language: Английский

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Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury

Experimental & Molecular Medicine, Journal Year: 2021, Volume and Issue: 53(2), P. 168 - 188

Published: Feb. 1, 2021

Abstract Advanced glycation end products (AGEs) are potentially harmful and heterogeneous molecules derived from nonenzymatic glycation. The pathological implications of AGEs ascribed to their ability promote oxidative stress, inflammation, apoptosis. Recent studies in basic translational research have revealed the contributing roles development progression various aging-related conditions, such as diabetes, cardiovascular complications, gut microbiome-associated illnesses, liver or neurodegenerative diseases, cancer. Excessive chronic and/or acute binge consumption alcohol (ethanol), a widely consumed addictive substance, is known cause more than 200 including use disorder (addiction), alcoholic disease, brain damage. However, despite considerable amount this area, underlying molecular mechanisms by which abuse causes cellular toxicity organ damage remain be further characterized. In review, we first briefly describe properties AGEs: formation, accumulation, receptor interactions. We then focus on causative functions that impact diseases. also highlight biological connection AGE–alcohol–adduct formations alcohol-mediated tissue injury. Finally, potential opportunities for treatment AGE- alcohol-related adduct-associated disorders according mechanistic insights presented.

Language: Английский

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Proteostasis of Islet Amyloid Polypeptide: A Molecular Perspective of Risk Factors and Protective Strategies for Type II Diabetes

Chemical Reviews, Journal Year: 2021, Volume and Issue: 121(3), P. 1845 - 1893

Published: Jan. 11, 2021

The possible link between hIAPP accumulation and β-cell death in diabetic patients has inspired numerous studies focusing on amyloid structures aggregation pathways of this hormone. Recent have reported the importance early oligomeric intermediates, many roles their interactions with lipid membrane, pH, insulin, zinc mechanism hIAPP. challenges posed by transient nature oligomers, structural heterogeneity, complex interaction membranes resulted development a wide range biophysical chemical approaches to characterize process. While cellular processes factors activating hIAPP-mediated cytotoxicity are still not clear, it recently been suggested that its impaired turnover processing proteasome autophagy may contribute significantly toward toxic and, eventually, death. Therefore, restoration proteostasis represent promising arena for design effective therapies. In review we discuss current knowledge pathology associated self-assembly point out opportunities therapy detailed biochemical, biophysical, understanding unveil.

Language: Английский

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Dietary polyphenols: regulate the advanced glycation end products-RAGE axis and the microbiota-gut-brain axis to prevent neurodegenerative diseases

Critical Reviews in Food Science and Nutrition, Journal Year: 2022, Volume and Issue: 63(29), P. 9816 - 9842

Published: May 19, 2022

Advanced glycation end products (AGEs) are formed in non-enzymatic reaction, oxidation, rearrangement and cross-linking between the active carbonyl groups of reducing sugars free amines amino acids. The Maillard reaction is related to sensory characteristics thermal processed food, while AGEs food matrix this process. a key link stress neurodegenerative disease. can interact with receptors for (RAGE), causing oxidative stress, inflammation response signal pathways activation diseases. Neurodegenerative diseases closely gut microbiota imbalance intestinal inflammation. Polyphenols multiple hydroxyl showed powerful ability scavenge ROS capture α-dicarbonyl species, which led formation mono- di- adducts, thereby inhibiting formation. be effectively prevented by production, interaction RAGEs, or regulating microbiota-gut-brain axis. These strategies include polyphenols multifunctional effects on inhibition, RAGE-ligand interactions blocking, abundance diversity microbiota, alleviation delay prevent progress. It wise promising strategy supplement dietary preventing via AGEs-RAGE axis regulation.

Language: Английский

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Multiomic signatures of body mass index identify heterogeneous health phenotypes and responses to a lifestyle intervention

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(4), P. 996 - 1008

Published: March 20, 2023

Multiomic profiling can reveal population heterogeneity for both health and disease states. Obesity drives a myriad of metabolic perturbations is risk factor multiple chronic diseases. Here we report an atlas cross-sectional longitudinal changes in 1,111 blood analytes associated with variation body mass index (BMI), as well multiomic associations host polygenic scores gut microbiome composition, from cohort 1,277 individuals enrolled wellness program (Arivale). Machine learning model predictions BMI multiomics captured heterogeneous phenotypic states metabolism composition better than BMI, which was also validated external (TwinsUK). Moreover, analyses identified variable trajectories different omics measures response to healthy lifestyle intervention; metabolomics-inferred decreased greater extent actual whereas proteomics-inferred exhibited resistance change. Our further analyte-analyte that were modified by partially reversed obesity during the intervention. Taken together, our findings provide molecular status, serving resource quantify predictive preventive medicine.

Language: Английский

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Prevention of Cardiovascular Disease in Type 1 Diabetes

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: 390(13), P. 1207 - 1217

Published: April 3, 2024

Language: Английский

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Damage-Associated Molecular Patterns in Myocardial Infarction and Heart Transplantation: The Road to Translational Success

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Dec. 8, 2020

In the setting of myocardial infarction (MI), ischemia reperfusion injury (IRI) occurs due to occlusion (ischemia) and subsequent re-establishment blood flow (reperfusion) a coronary artery. A similar phenomenon is observed in heart transplantation (HTx) when, after cold storage, donor connected recipient's circulation. Although essential for survival cardiomyocytes, it paradoxically leads additional damage experimental MI HTx models. Damage (or danger)-associated molecular patterns (DAMPs) are endogenous molecules released cellular or stress such as IRI. DAMPs activate pattern recognition receptors (PRRs), set motion complex signaling cascade resulting release cytokines profound inflammatory reaction. This response thought function double-edged sword. enables removal cell debris promotes wound healing, DAMP mediated signalling can also exacerbate state disproportional matter, thereby leading tissue damage. Upon MI, this expansion infarcted area deterioration cardiac preclinical Eventually culminates adverse remodeling; process that increased fibrosis, gradual further loss left ventricular dilation failure. HTx, aggravate ischemic damage, which results more pronounced impacts increases occurrence primary graft dysfunction rejection via cytokine release, edema, enhanced myocardial/endothelial allograft fibrosis. Therapies targeting PRRs have predominantly been investigated models potentially cardioprotective. To date, however, none these interventions reached clinical arena. review we summarize current evidence involvement HTx. Furthermore, will discuss various therapeutic approaches interplay provide possible reasons why translation still fails.

Language: Английский

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Advanced glycation end products in diabetes, cancer and phytochemical therapy

Drug Discovery Today, Journal Year: 2020, Volume and Issue: 25(9), P. 1614 - 1623

Published: July 8, 2020

Language: Английский

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Aldose Reductase: An Emerging Target for Development of Interventions for Diabetic Cardiovascular Complications

Frontiers in Endocrinology, Journal Year: 2021, Volume and Issue: 12

Published: March 11, 2021

Diabetes is a leading cause of cardiovascular morbidity and mortality. Despite numerous treatments for disease (CVD), patients with diabetes, these therapies provide less benefit protection from CVD. These considerations spur the concept that diabetes-specific, disease-modifying are essential to identify especially as diabetes epidemic continues expand. In this context, high levels blood glucose stimulate flux via aldose reductase (AR) pathway metabolic signaling changes in cells system. animal models AR hearts increased by ischemia its inhibition protects diabetic non-diabetic ischemia-reperfusion injury. mouse atherosclerosis, human expression accelerates progression impairs regression atherosclerotic plaques. Genetic studies have revealed single nucleotide polymorphisms (SNPs) ALD2 ( gene ) associated complications, including cardiorenal complications. This Review presents current knowledge regarding roles causes consequences status inhibitors clinical trials. Studies both subjects presented highlight breadth evidence linking diabetes.

Language: Английский

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