keyword
https://read.qxmd.com/read/38394622/from-a-droplet-to-a-fibril-and-from-a-fibril-to-a-droplet-intertwined-transition-pathways-in-highly-dynamic-enzyme-modulated-peptide-adenosine-triphosphate-systems
#21
JOURNAL ARTICLE
Robert Dec, Wojciech Dzwolak, Roland Winter
Many cellular coassemblies of proteins and polynucleotides facilitate liquid-liquid phase separation (LLPS) and the subsequent self-assembly of disease-associated amyloid fibrils within the liquid droplets. Here, we explore the dynamics of coupled phase and conformational transitions of model adenosine triphosphate (ATP)-binding peptides, ACC1-13 K n , consisting of the potent amyloidogenic fragment of insulin's A-chain (ACC1-13 ) merged with oligolysine segments of various lengths (K n , n = 16, 24, 40). The self-assembly of ATP-stabilized amyloid fibrils is preceded by LLPS for peptides with sufficiently long oligolysine segments...
February 23, 2024: Journal of the American Chemical Society
https://read.qxmd.com/read/38393902/pericyte-control-of-gene-expression-in-the-blood-brain-barrier-endothelium-implications-for-alzheimer-s-disease
#22
JOURNAL ARTICLE
Doug Nelson, Kevin J Thompson, Lushan Wang, Zengtao Wang, Paulina Eberts, Samira M Azarin, Krishna R Kalari, Karunya K Kandimalla
BACKGROUND: A strong body of evidence suggests that cerebrovascular pathologies augment the onset and progression of Alzheimer's disease (AD). One distinctive aspect of this cerebrovascular dysfunction is the degeneration of brain pericytes-often overlooked supporting cells of blood-brain barrier endothelium. OBJECTIVE: The current study investigates the influence of pericytes on gene and protein expressions in the blood-brain barrier endothelium, which is expected to facilitate the identification of pathophysiological pathways that are triggered by pericyte loss and lead to blood-brain barrier dysfunction in AD...
February 19, 2024: Journal of Alzheimer's Disease: JAD
https://read.qxmd.com/read/38379904/a-review-of-the-mechanisms-of-abnormal-ceramide-metabolism-in-type-2-diabetes-mellitus-alzheimer-s-disease-and-their-co-morbidities
#23
REVIEW
Yun Pan, Jieying Li, Panjie Lin, Lihua Wan, Yiqian Qu, Lingyong Cao, Lei Wang
The global prevalence of type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) is rapidly increasing, revealing a strong association between these two diseases. Currently, there are no curative medication available for the comorbidity of T2DM and AD. Ceramides are structural components of cell membrane lipids and act as signal molecules regulating cell homeostasis. Their synthesis and degradation play crucial roles in maintaining metabolic balance in vivo , serving as important mediators in the development of neurodegenerative and metabolic disorders...
2024: Frontiers in Pharmacology
https://read.qxmd.com/read/38379184/associations-of-serum-insulin-and-related-measures-with-neuropathology-and-cognition-in-older-persons-with-and-without-diabetes
#24
JOURNAL ARTICLE
Zoe Arvanitakis, Ana W Capuano, Han Tong, Rupal I Mehta, Frederick Anokye-Danso, David A Bennett, Steven E Arnold, Rexford S Ahima
OBJECTIVE: To examine associations of serum insulin and related measures with neuropathology and cognition in older persons. METHODS: We studied 192 older persons (96 with diabetes and 96 without, matched by sex and balanced by age-at-death, education, and postmortem interval) from a community-based, clinical-pathologic study of aging, with annual evaluations including neuropsychological testing (summarized into global cognition and 5 cognitive domains) and postmortem autopsy...
February 20, 2024: Annals of Neurology
https://read.qxmd.com/read/38366875/ains-insulin-type-amyloidoma-of-the-extremity-diagnosed-by-fine-needle-aspiration
#25
JOURNAL ARTICLE
Nisha S Ramani, Rhea A Morani, Bhuvaneswari Krishnan
Amyloid is an extracellular deposition of Congo red positive material which shows apple green birefringence under polarized light. A cytopathologist can uncommonly encounter such cases. Among the reported cases, a fine-needle aspiration (FNA) of amyloid is frequently misinterpreted as acellular nondiagnostic material. We report a case of amyloidoma of the right upper arm in a 68-year-old man with history of renal transplantation for diabetic nephropathy who presented with loss of appetite and weight loss. Physical exam showed a 7 cm hard nodular subcutaneous mass in the right upper arm...
February 17, 2024: Diagnostic Cytopathology
https://read.qxmd.com/read/38365968/efficient-inhibition-of-amyloid-fibrillation-and-cytotoxicity-of-%C3%AE-synuclein-and-human-insulin-using-biosynthesized-silver-nanoparticles-decorated-by-green-tea-polyphenols
#26
JOURNAL ARTICLE
Behnaz Mirzaei-Behbahani, Ali Akbar Meratan, Beitollah Moosakhani, Mahya Mohammad-Zaheri, Zahra Mousavi-Jarrahi, Nasser Nikfarjam, Mohammad Bagher Shahsavani, Ali Akbar Saboury
Green tea polyphenols (GTPs), particularly epigallocatechin-3-gallate, stand out among natural small molecules screened for their ability to target protein aggregates due to their potent anti-amyloidogenic and neuroprotective activities against various disease-related peptides and proteins. However, the clinical applications of GTPs in amyloid-related diseases have been greatly limited by drawbacks such as poor chemical stability and low bioavailability. To address these limitations, this study utilized an Iranian green tea polyphenolic extract as a reducing agent to neutralize silver ions and facilitate the formation of silver nanoparticle capped by GTPs (GTPs-capped AgNPs)...
February 16, 2024: Scientific Reports
https://read.qxmd.com/read/38365278/serum-biomarker-signature-is-predictive-of-the-risk-of-hepatocellular-cancer-in-patients-with-cirrhosis
#27
JOURNAL ARTICLE
Hashem El-Serag, Fasiha Kanwal, Jing Ning, Hannah Powell, Saira Khaderi, Amit G Singal, Sumeet Asrani, Jorge A Marrero, Christopher I Amos, Aaron P Thrift, Michelle Luster, Abeer Alsarraj, Luis Olivares, Darlene Skapura, Jenny Deng, Emad Salem, Omar Najjar, Xian Yu, Hao Duong, Michael E Scheurer, Christie M Ballantyne, Salma Kaochar
BACKGROUND: Inflammatory and metabolic biomarkers have been associated with hepatocellular cancer (HCC) risk in phases I and II biomarker studies. We developed and internally validated a robust metabolic biomarker panel predictive of HCC in a longitudinal phase III study. METHODS: We used data and banked serum from a prospective cohort of 2266 adult patients with cirrhosis who were followed until the development of HCC (n=126). We custom designed a FirePlex immunoassay to measure baseline serum levels of 39 biomarkers and established a set of biomarkers with the highest discriminatory ability for HCC...
February 16, 2024: Gut
https://read.qxmd.com/read/38361318/association-of-cigarette-smoking-with-cerebrospinal-fluid-biomarkers-of-insulin-sensitivity-and-neurodegeneration
#28
JOURNAL ARTICLE
Fan Wang, Hui Li, Tiantian Kong, Ligang Shan, Jiajia Guo, Yan Wu, Xingguang Luo, Senthil Kumaran Satyanarayanan, Kuan-Pin Su, Yanlong Liu
INTRODUCTION: Cigarette smoking increases both the risk for insulin resistance and amyloid-β (Aβ) aggregation, and impaired brain insulin/insulin-like growth factor 1 (IGF1) signaling might increase risk factors for Alzheimer's disease (AD). We aimed to investigate the association among cerebrospinal fluid (CSF) insulin sensitivity/IGF1, glucose/lactate, and Aβ42 and further explore whether insulin sensitivity contributed to the risk for AD in active smokers. METHODS: In this cross-sectional study, levels of insulin, IGF1, and lactate/glucose of 75 active smokers and 78 nonsmokers in CSF were measured...
February 2024: Brain and Behavior
https://read.qxmd.com/read/38353782/a-colorimetric-immunoassay-for-the-detection-of-human-vascular-endothelial-growth-factor-165-vegf-165-based-on-anti-vegf-iron-oxide-nanoparticle-conjugation
#29
JOURNAL ARTICLE
Hülya Kuduğ Ceylan, Fatma Öztürk Kırbay, İdris Yazgan, Murat Elibol
Vascular endothelial growth factor (VEGF) is an indispensable element in many physiological processes, while alterations in its level in the circulating system are signs of pathology-associated diseases. Therefore, its precise and selective detection is critical for clinical applications to monitor the progression of the pathology. In this study, an optical immunoassay biosensor was developed as a model study for detecting recombinant VEGF165 . The VEGF165 sample was purified from recombinant Kluyveromyces lactis GG799 yeast cells...
February 14, 2024: Mikrochimica Acta
https://read.qxmd.com/read/38333746/metformin-improves-memory-via-ampk-mtor-dependent-route-in-a-rat-model-of-alzheimer-s-disease
#30
JOURNAL ARTICLE
Reza Ale Mahmoud Mehraban, Parvin Babaei, Kambiz Rohampour, Adele Jafari, Zoleikha Golipoor
OBJECTIVES: Metformin, as an insulin sensitizer, is a familiar antidiabetic drug. Increasing evidence points to metformin's protective effects against Alzheimer's disease (AD). However, the mechanism is not well understood. The present study evaluated whether inhibiting AMPK and activating mTOR could stop metformin from improving memory in rats with streptozotocin (STZ) -induced Alzheimer's disease. MATERIALS AND METHODS: Twelve-week-old Wistar rats, were injected 3 mg/kg STZ intracerebroventricularly on days 1 and 3 to develop the animal model...
2024: Iranian Journal of Basic Medical Sciences
https://read.qxmd.com/read/38317568/protective-effect-of-extractive-and-biotechnological-chondroitin-in-insulin-amyloid-and-advanced-glycation-end-product-induced-toxicity
#31
(no author information available yet)
No abstract text is available yet for this article.
February 5, 2024: Journal of Cellular Physiology
https://read.qxmd.com/read/38304364/hippocampal-ganglioside-composition-is-altered-by-metformin-and-liraglutide-treatment-in-a-high-fat-high-sugar-diet-rat-model
#32
JOURNAL ARTICLE
Marin Kuharić, Vedrana Ivić, Milorad Zjalić, Anita Matić, Ines Drenjančević, Sandor G Vari, Aleksandar Včev, Marija Heffer
Insulin resistance has many deleterious effects on the central nervous system, including the initiation and potentiation of neurodegeneration. While the pathogenesis of Alzheimer's disease has been extensively researched with many insights into the effects of amyloids and neurofibrillary tangles, the connection between the two pathogenic entities has not yet been fully elucidated. Gangliosides are commonly found in neuronal membranes and myelin, specifically in lipid rafts that have been linked to pathological amyloidogenesis...
April 2023: Acta Clinica Croatica
https://read.qxmd.com/read/38301805/mechanistic-modeling-of-amyloid-oligomer-and-protofibril-formation-in-bovine-insulin
#33
JOURNAL ARTICLE
Keisuke Yuzu, Hiroshi Imamura, Takuro Nozaki, Yuki Fujii, Shaymaa Mohamed Mohamed Badawy, Ken Morishima, Aya Okuda, Rintaro Inoue, Masaaki Sugiyama, Eri Chatani
Early phase of amyloid formation, where prefibrillar aggregates such as oligomers and protofibrils are often observed, is crucial for understanding pathogenesis. However, the detailed mechanisms of their formation have been difficult to elucidate because they tend to form transiently and heterogeneously. Here, we found that bovine insulin protofibril formation proceeds in a monodisperse manner, which allowed us to characterize the detailed early aggregation process by light scattering in combination with thioflavin T (ThT) fluorescence and Fourier transform infrared (FTIR) spectroscopy...
January 30, 2024: Journal of Molecular Biology
https://read.qxmd.com/read/38290839/cardiometabolic-risk-factors-and-neurodegeneration-a-review-of-the-mechanisms-underlying-diabetes-obesity-and-hypertension-in-alzheimer-s-disease
#34
REVIEW
Vijay Patel, Paul Edison
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 and can accelerate neurodegeneration and perpetuate the burden of AD. Insulin resistance and enzymes including insulin degrading enzymes are implicated in AD where breakdown of insulin is prioritised over amyloid-β. Leptin resistance and inflammation demonstrated by higher plasma and central nervous system levels of interleukin-6 (IL-6), IL-1β and tumour necrosis factor-α, are mechanisms connecting obesity and diabetes with AD...
January 30, 2024: Journal of Neurology, Neurosurgery, and Psychiatry
https://read.qxmd.com/read/38256230/a-cross-sectional-study-of-alzheimer-related-proteins-in-women-with-polycystic-ovary-syndrome
#35
JOURNAL ARTICLE
Alexandra E Butler, Abu Saleh Md Moin, Thozhukat Sathyapalan, Stephen L Atkin
Polycystic ovary syndrome (PCOS) is the most common endocrine condition in women of reproductive age, and several risk factors found in PCOS are associated with an increased risk of Alzheimer's disease (AD). Proteins increased in AD have been reported to include fibronectin (FN) fragments 3 and 4 (FN1.3 and FN1.4, respectively) and ApoE. We hypothesized that Alzheimer-related proteins would be dysregulated in PCOS because of associated insulin resistance and obesity. In this comparative cross-sectional analysis, aptamer-based SomaScan proteomic analysis for the detection of plasma Alzheimer-related proteins was undertaken in a PCOS biobank of 143 women with PCOS and 97 control women...
January 18, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38242039/hif-1%C3%AE-serves-as-a-co-linker-between-ad-and-t2dm
#36
REVIEW
Yang Hai, Ke Ren, Yarong Zhang, Lili Yang, Haoshi Cao, Xianxia Yuan, Linling Su, Hailong Li, Xiaoli Feng, Dongling Liu
Alzheimer's disease (AD)-related brain deterioration is linked to the type 2 diabetes mellitus (T2DM) features hyperglycemia, hyperinsulinemia, and insulin resistance. Hypoxia as a common risk factor for both AD and T2DM. Hypoxia-inducible factor-1 alpha (HIF-1α) acts as the main regulator of the hypoxia response and may be a key target in the comorbidity of AD and T2DM. HIF-1α expression is closely related to hyperglycemia, insulin resistance, and inflammation. Tissue oxygen consumption disrupts HIF-1α homeostasis, leading to increased reactive oxygen species levels and the inhibition of insulin receptor pathway activity, causing neuroinflammation, insulin resistance, abnormal Aβ deposition, and tau hyperphosphorylation...
February 2024: Biomedicine & Pharmacotherapy
https://read.qxmd.com/read/38222463/modelling-alzheimer-s-disease-in-a-dish-dissecting-amyloid-%C3%AE-metabolism-in-human-neurons
#37
COMMENT
Elizabeth Hill, Thomas J Cunningham
This scientific commentary refers to 'Inhibition of insulin-degrading enzyme in human neurons promotes amyloid-β deposition' by Rowland et al. (https://doi.org/10.1042/NS20230016). Insulin-degrading enzyme (IDE) and neprilysin (NEP) have been proposed as two Aβ-degrading enzymes supported by human genetics and in vivo data. Rowland et al. provide complementary evidence of a key role for IDE in Aβ metabolism in human-induced pluripotent stem cell (iPSC)-derived cortical neurons.
January 2024: Neuronal Signaling
https://read.qxmd.com/read/38218538/ripk3-promotes-islet-amyloid-induced-%C3%AE-cell-loss-and-glucose-intolerance-in-a-humanized-mouse-model-of-type-2-diabetes
#38
JOURNAL ARTICLE
Noyonika Mukherjee, Christopher J Contreras, Li Lin, Kaitlyn A Colglazier, Egan G Mather, Michael A Kalwat, Nathalie Esser, Steven E Kahn, Andrew T Templin
OBJECTIVE: Aggregation of human islet amyloid polypeptide (hIAPP), a β-cell secretory product, leads to islet amyloid deposition, islet inflammation and β-cell loss in type 2 diabetes (T2D), but the mechanisms that underlie this process are incompletely understood. Receptor interacting protein kinase 3 (RIPK3) is a pro-death signaling molecule that has recently been implicated in amyloid-associated brain pathology and β-cell cytotoxicity. Here, we evaluated the role of RIPK3 in amyloid-induced β-cell loss using a humanized mouse model of T2D that expresses hIAPP and is prone to islet amyloid formation...
January 11, 2024: Molecular Metabolism
https://read.qxmd.com/read/38215274/screening-of-novel-biomarkers-for-acute-kidney-transplant-rejection-using-dia-ms-based-proteomics
#39
JOURNAL ARTICLE
Ce Wang, Gang Feng, Jie Zhao, Yang Xu, Yang Li, Lin Wang, Meng Wang, Miao Liu, Yilin Wang, Hong Mu, Chunlei Zhou
BACKGROUND: Kidney transplantation is the preferred treatment for patients with end-stage renal disease. However, acute rejection poses a threat to the graft long-term survival. The aim of this study was to identify novel biomarkers to detect acute kidney transplant rejection. METHODS: The serum proteomic profiling of kidney transplant patients with T cell-mediated acute rejection (TCMR) and stable allograft function (STA) was analyzed using data-independent acquisition mass spectrometry (DIA-MS)...
January 12, 2024: Proteomics. Clinical Applications
https://read.qxmd.com/read/38211368/the-influence-of-zwitterionic-and-anionic-phospholipids-on-protein-aggregation
#40
REVIEW
Abid Ali, Tianyi Dou, Aidan P Holman, Andrew Hung, Luke Osborne, Davis Pickett, Axell Rodriguez, Kiryl Zhaliazka, Dmitry Kurouski
The progressive aggregation of misfolded proteins is the underlying molecular cause of numerous pathologies including Parkinson's disease and injection and transthyretin amyloidosis. A growing body of evidence indicates that protein deposits detected in organs and tissues of patients diagnosed with such pathologies contain fragments of lipid membranes. In vitro experiments also showed that lipid membranes could strongly change the aggregation rate of amyloidogenic proteins, as well as alter the secondary structure and toxicity of oligomers and fibrils formed in their presence...
January 7, 2024: Biophysical Chemistry
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