Browsing all papers, sorted by Most cited. Showing 25 of 39,449.
Exosome RNA Unshielding Couples Stromal Activation to Pattern Recognition Recep…
Interactions between stromal fibroblasts and cancer cells generate signals for cancer progression, therapy resistance, and inflammatory responses. Although endogenous RNAs acting as damage-associated molecular patterns (DAMPs) for pattern recognition receptors (PRRs) may represent one such signal, these RNAs must remain unrecognized under non-pathological co…
["Breast Neoplasms""DEAD Box Protein 58""Exosomes""Humans"Integrated multimodal cell atlas of Alzheimer’s disease
Alzheimer's disease (AD) is the most common cause of dementia in older adults. Neuropathological and imaging studies have demonstrated a progressive and stereotyped accumulation of protein aggregates, but the underlying molecular and cellular mechanisms driving AD progression and vulnerable cell populations affected by disease remain coarsely understood. The…
Gut-derived bacterial vesicles carrying lipopolysaccharide promote microglia-me…
INTRODUCTION: Growing evidence links gut microbiota (GM) to Alzheimer's disease (AD). Elevated lipopolysaccharide (LPS) levels, a Gram-negative bacteria component, are found in AD brains, but how LPS breaches the blood-brain barrier (BBB) remains unclear. Hypotheses suggest that bacteria-derived extracellular vesicles (bEVs) may transport LPS across the BBB.…
["Lipopolysaccharides""Microglia""Humans""Gastrointestinal Microbiome"Depression as a risk factor for Alzheimer's disease: Genes, steroids, cytokines…
Depression (MDD) is prodromal to, and a component of, Alzheimer's disease (AD): it may also be a trigger for incipient AD. MDD is not a unitary disorder, so there may be particular subtypes of early life MDD that pose independent high risks for later AD, though the identification of these subtypes is problematical. There may either be a common pathological e…
["Alzheimer Disease""Cytokines""Major Depressive Disorder""EpigenesisSingle-cell multiregion epigenomic rewiring in Alzheimer's disease progression…
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, yet its epigenetic underpinnings remain elusive. Here, we generate and integrate single-cell epigenomic and transcriptomic profiles of 3.5 million cells from 384 postmortem brain samples across 6 regions in 111 AD and control individuals. We identify over…
["Alzheimer Disease""Humans""Single-Cell Analysis""Disease Progression"Ischemia-induced upregulation of autophagy preludes dysfunctional lysosomal sto…
1. Autophagy. 2021 Jun;17(6):1519-1542. doi: 10.1080/15548627.2020.1840796. Epub 2020 Nov 12. Ischemia-induced upregulation of autophagy preludes dysfunctional lysosomal storage and associated synaptic impairments in neurons. Zhang X(1), Wei M(1), Fan J(1), Yan W(1), Zha X(1), Song H(1), Wan R(1), Yin Y(1), Wang W(1). Author information: (1)Department of Phy…
Functional assessments through novel proteomics approaches: Application to insu…
BACKGROUND: Events that instigate disease may involve biochemical events distinct from changes in the steady-state levels of proteins. Even chronic degenerative disorders appear to involve changes such as post-translational modifications. NEW METHOD: We have begun a series of proteomics analyses on proteins that have been fractionated by functional status. B…
["Alzheimer Disease""Amyloid beta-Peptides""Animals""AnimalsOpioid Receptors.
Opioids are the oldest and most potent drugs for the treatment of severe pain. Their clinical application is undisputed in acute (e.g., postoperative) and cancer pain, but their long-term use in chronic pain has met increasing scrutiny. This article reviews mechanisms underlying opioid analgesia and other opioid actions. It discusses the structure, function,…
["AnalgesicsOpioid""Chronic Pain""Drug Tolerance"Utilization of fluid-based biomarkers as endpoints in disease-modifying clinica…
BACKGROUND: Clinical trials in Alzheimer's disease (AD) had high failure rates for several reasons, including the lack of biological endpoints. Fluid-based biomarkers may present a solution to measure biologically relevant endpoints. It is currently unclear to what extent fluid-based biomarkers are applied to support drug development. METHODS: We systematica…
["Alzheimer Disease""Humans""Biomarkers""Clinical Trials as Topic"Microglia-mediated IGF-I neuroprotection in the rd10 mouse model of retinitis p…
PURPOSE: To characterize the effect of IGF-I in the rd10 mouse model of retinitis pigmentosa at the cellular level, focusing on the role of microglia in the neurodegenerative process. METHODS: Both organotypic retinal explants and intravitreal injections were used to assess the effect of IGF-I on photoreceptor cell death in the Pde6b(rd10) mice. Cell death w…
["Animals""Apoptosis""CD11b Antigen""Calcium-Binding Proteins"The Role of Complement in Synaptic Pruning and Neurodegeneration.
The complement system, an essential part of the innate immune system, is composed of a group of secreted and membrane proteins that collectively participate in maintaining the function of the healthy and diseased brain. However, an inappropriate activation of the complement system has been related to an inflammatory response in multiple diseases, such as str…
IGF2BP1 exacerbates neuroinflammation and cerebral ischemia/reperfusion injury…
BACKGROUND: Cerebral ischemia/reperfusion (I/R) injury induces neuronal ferroptosis and microglial phenotypic shifts, driving post-ischemic neurological deficits. This study examines the regulatory role of the N6-methyladenosine (m6A) reader insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in coordinating these pathological processes through Kea…
["Animals""Ferroptosis""Microglia""Reperfusion Injury"Detailed stratified GWAS analysis for severe COVID-19 in four European populati…
Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with…
["Humans""COVID-19""SARS-CoV-2""Genome-Wide Association Study"The Molecular Mechanisms of Cognitive Dysfunction in Long COVID: A Narrative Re…
Cognitive dysfunction represents one of the most persistent and disabling features of Long COVID, yet its molecular underpinnings remain incompletely understood. This narrative review synthesizes current evidence on the pathophysiological mechanisms linking SARS-CoV-2 infection to long-term neurocognitive sequelae. Key processes include persistent neuroinfla…
["Humans""COVID-19""Cognitive Dysfunction""SARS-CoV-2"Histone Deacetylases 1 and 2 Regulate Microglia Function during Development, Ho…
Microglia as tissue macrophages contribute to the defense and maintenance of central nervous system (CNS) homeostasis. Little is known about the epigenetic signals controlling microglia function in vivo. We employed constitutive and inducible mutagenesis in microglia to delete two class I histone deacetylases, Hdac1 and Hdac2. Prenatal ablation of Hdac1 and…
["Animals""Apoptosis""Cell Proliferation""Disease ModelsComplement C1q-Targeted Microglial Membrane Camouflaged Nanolipid Carriers for…
Aberrant activation of the complement system drives early synaptic loss and chronic neuroinflammation in Alzheimer's disease (AD). Here, we identified complement component C1q as a key upregulated target in AD and screened Alectinib (ALE), an FDA-approved kinase inhibitor, as a high-affinity C1q binder. To achieve brain-targeted delivery, ALE was encapsulate…
["Animals""Alzheimer Disease""Microglia""Mice"Cerium-doped Prussian blue biomimetic nanozyme as an amplified pyroptosis inhib…
Antioxidant enzyme therapy shows promise for treating Alzheimer's disease (AD), but significant challenges remain in achieving effective blood-brain barrier (BBB) penetration and sustained therapeutic effects. We developed a novel neutrophil membrane (NM)-coated cerium-doped Prussian blue biomimetic nanozyme (NM@PB-Ce) that demonstrates outstanding enzymatic…
["Cerium""Animals""Alzheimer Disease""Amyloid beta-Peptides"Insulin-Like Growth Factor Signaling in Alzheimer's Disease: Pathophysiology an…
Alzheimer's disease (AD) is the leading cause of dementia among the elderly population, posing a significant public health challenge due to limited therapeutic options that merely delay cognitive decline. AD is associated with impaired energy metabolism and reduced neurotrophic signaling. The insulin-like growth factor (IGF) signaling pathway, crucial for ce…
["Alzheimer Disease""Insulin-Like Growth Factor I""Insulin-Like Growth Factor II""Insulin-Like Growth Factor Binding Proteins"Pseudostellaria heterophylla polysaccharide mitigates Alzheimer's-like patholog…
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by neuroinflammation, for which gut dysbiosis may be implicated. Our previous study showed that treatment with Pseudostellaria heterophylla aqueous extract and one of its cyclopeptides, heterophyllin B, attenuate memory deficits via immunomodulation and neurite regeneration. H…
["Animals""Alzheimer Disease""Gastrointestinal Microbiome""Polysaccharides"Caloric restriction.
Restricting the intake of calories has been practiced as a method for increasing both the length and quality of life for over 500 years. Experimental work confirming the success of this approach in animals has accumulated over the last 100 years. Lifelong caloric restriction (CR) may extend life by up to 50% in rodents, with progressively less impact the lat…
["Animals""Caloric Restriction""Cardiovascular Diseases""Diabetes MellitusSystemic inflammation as a central player in the initiation and development of…
Alzheimer's disease (AD) is an age-related neurodegenerative disorder and the most common cause of dementia. While the amyloid cascade hypothesis has long dominated AD research, emerging evidence suggests that neuroinflammation may play a more central role in disease onset and progression. Increasingly, AD is recognized as a multifactorial disorder influence…
Young adult microglial deletion of C1q reduces engulfment of synapses and preve…
C1q is a multifunctional protein, including its role as the initiating protein of the classical complement cascade. While classical pathway activation is involved in synaptic pruning during development of the nervous system, it also contributes to enhanced inflammation and cognitive decline in Alzheimer's disease (AD). Constitutive genetic C1q deficiency has…
Neuronal functions of FOXO/DAF-16.
The FOXO family of transcription factors plays a conserved role in longevity and tissue homeostasis across species. In the mammalian nervous system, emerging evidence has implicated FOXOs in cognitive performance, stem cell maintenance, regeneration, and protection against stress. Much of what we know about neuronal functions of FOXO emerged from recent stud…
Interactions between antidiabetes medications and heart-brain axis.
PURPOSE OF REVIEW: The heart - brain axis (HBA) is the physiological interactions between the cardiovascular and nervous systems through autonomic nerves, hormones, and cytokines. Patients diagnosed with diabetes mellitus have an increased risk of the cardiovascular and neurological diseases. However, recent evidence demonstrated that different antidiabetic…
["Humans""Hypoglycemic Agents""Brain""Heart"Trigeminal neuralgia.
Trigeminal neuralgia (TN) is a facial pain disorder characterized by intense and paroxysmal pain that profoundly affects quality of life and presents complex challenges in diagnosis and treatment. TN can be categorized as classical, secondary and idiopathic. Epidemiological studies show variable incidence rates and an increased prevalence in women and in the…
["Trigeminal Neuralgia""Humans""Carbamazepine""Quality of Life"