Luteolin inhibits herpes simplex virus 1 infection by activating cyclic guanosine monophosphate-adenosine monophosphate synthase-mediated antiviral innate immunity DOI
Yuan Wang, Feng Li, Zexu Wang

et al.

Phytomedicine, Journal Year: 2023, Volume and Issue: 120, P. 155020 - 155020

Published: Aug. 17, 2023

Language: Английский

Virus exposure and neurodegenerative disease risk across national biobanks DOI Creative Commons
Kristin Levine, Hampton L. Leonard, Cornelis Blauwendraat

et al.

Neuron, Journal Year: 2023, Volume and Issue: 111(7), P. 1086 - 1093.e2

Published: Jan. 19, 2023

Language: Английский

Citations

212

Recent advances in Alzheimer’s disease: Mechanisms, clinical trials and new drug development strategies DOI Creative Commons
Jifa Zhang, Yinglu Zhang, Jiaxing Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 23, 2024

Abstract Alzheimer’s disease (AD) stands as the predominant form of dementia, presenting significant and escalating global challenges. Its etiology is intricate diverse, stemming from a combination factors such aging, genetics, environment. Our current understanding AD pathologies involves various hypotheses, cholinergic, amyloid, tau protein, inflammatory, oxidative stress, metal ion, glutamate excitotoxicity, microbiota-gut-brain axis, abnormal autophagy. Nonetheless, unraveling interplay among these pathological aspects pinpointing primary initiators require further elucidation validation. In past decades, most clinical drugs have been discontinued due to limited effectiveness or adverse effects. Presently, available primarily offer symptomatic relief often accompanied by undesirable side However, recent approvals aducanumab ( 1 ) lecanemab 2 Food Drug Administration (FDA) present potential in disrease-modifying Nevertheless, long-term efficacy safety need Consequently, quest for safer more effective persists formidable pressing task. This review discusses pathogenesis, advances diagnostic biomarkers, latest updates trials, emerging technologies drug development. We highlight progress discovery selective inhibitors, dual-target allosteric modulators, covalent proteolysis-targeting chimeras (PROTACs), protein-protein interaction (PPI) modulators. goal provide insights into prospective development application novel drugs.

Language: Английский

Citations

197

Cerebral dysfunctions caused by sepsis during ageing DOI Open Access
Tatsuya Manabe, Michael T. Heneka

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 22(7), P. 444 - 458

Published: Nov. 11, 2021

Language: Английский

Citations

115

Inflammation at the crossroads of COVID-19, cognitive deficits and depression DOI

Natalia M. Lyra e Silva,

Fernanda G. Q. Barros‐Aragão, Fernanda G. De Felice

et al.

Neuropharmacology, Journal Year: 2022, Volume and Issue: 209, P. 109023 - 109023

Published: March 4, 2022

Language: Английский

Citations

80

Compartmentalized ocular lymphatic system mediates eye–brain immunity DOI Creative Commons
Xiangyun Yin, Sophia Zhang, Ju-Hyun Lee

et al.

Nature, Journal Year: 2024, Volume and Issue: 628(8006), P. 204 - 211

Published: Feb. 28, 2024

Abstract The eye, an anatomical extension of the central nervous system (CNS), exhibits many molecular and cellular parallels to brain. Emerging research demonstrates that changes in brain are often reflected particularly retina 1 . Still, possibility immunological nexus between posterior eye rest CNS tissues remains unexplored. Here, studying immune responses herpes simplex virus brain, we observed intravitreal immunization protects mice against intracranial viral challenge. This protection extended bacteria even tumours, allowing therapeutic glioblastoma through immunization. We further show anterior compartments have distinct lymphatic drainage systems, with latter draining deep cervical lymph nodes vasculature optic nerve sheath. drainage, like meningeal lymphatics, could be modulated by stimulator VEGFC. Conversely, inhibition signalling on overcome a major limitation gene therapy diminishing response adeno-associated ensuring continued efficacy after multiple doses. These results reveal shared circuit able mount unified highlighting understudied feature opening up potential for new strategies ocular diseases.

Language: Английский

Citations

42

Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders DOI Creative Commons
Jessica R. Cohen,

Annette Mathew,

Kirk D. Dourvetakis

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(6), P. 511 - 511

Published: March 14, 2024

Neuroinflammatory and neurodegenerative disorders including Alzheimer’s disease (AD), Parkinson’s (PD), traumatic brain injury (TBI) Amyotrophic lateral sclerosis (ALS) are chronic major health disorders. The exact mechanism of the neuroimmune dysfunctions these pathogeneses is currently not clearly understood. These show dysregulated inflammatory responses, activation neurons, glial cells, neurovascular unit damage associated with excessive release proinflammatory cytokines, chemokines, neurotoxic mediators, infiltration peripheral immune cells into brain, as well entry mediators through damaged endothelial blood–brain barrier tight junction proteins. Activation leads to many molecules that cause neuroinflammation neurodegeneration. Gulf War Illness (GWI) myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) also dysfunctions. Currently, there no effective disease-modifying therapeutic options available for diseases. Human induced pluripotent stem cell (iPSC)-derived astrocytes, microglia, pericytes used models drug discovery. This review highlights certain recent trends in neuroinflammatory responses iPSC-derived applications

Language: Английский

Citations

38

Updates in Alzheimer's disease: from basic research to diagnosis and therapies DOI Creative Commons

Enjie Liu,

Yao Zhang,

Jian–Zhi Wang

et al.

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Sept. 4, 2024

Language: Английский

Citations

19

Anti-herpetic tau preserves neurons via the cGAS-STING-TBK1 pathway in Alzheimer’s disease DOI Creative Commons

Vanesa R. Hyde,

Chaoming Zhou,

J R Muñóz y Fernández

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: unknown, P. 115109 - 115109

Published: Jan. 1, 2025

Alzheimer's disease (AD) diagnosis relies on the presence of extracellular β-amyloid (Aβ) and intracellular hyperphosphorylated tau (p-tau). Emerging evidence suggests a potential link between AD pathologies infectious agents, with herpes simplex virus 1 (HSV-1) being leading candidate. Our investigation, using metagenomics, mass spectrometry, western blotting, decrowding expansion pathology, detects HSV-1-associated proteins in human brain samples. Expression herpesvirus protein ICP27 increases severity strongly colocalizes p-tau but not Aβ. Modeling organoids shows that HSV-1 infection elevates phosphorylation. Notably, reduces expression markedly decreases post-infection neuronal death from 64% to 7%. This modeling prompts investigation into cGAS-STING-TBK1 pathway products, nuclear factor (NF)-κB IRF-3, which AD. Furthermore, experimental activation STING enhances phosphorylation, while TBK1 inhibition prevents it. Together, these findings suggest phosphorylation acts as an innate immune response AD, driven by cGAS-STING.

Language: Английский

Citations

11

The Importance of CXCL1 in Physiology and Noncancerous Diseases of Bone, Bone Marrow, Muscle and the Nervous System DOI Open Access
Jan Korbecki, Magdalena Gąssowska-Dobrowolska,

Jerzy Wójcik

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(8), P. 4205 - 4205

Published: April 11, 2022

This review describes the role of CXCL1, a chemokine crucial in inflammation as chemoattractant for neutrophils, physiology and selected major non-cancer diseases. Due to vast amount available information, we focus on CXCL1 plays bones, bone marrow, muscle nervous system. For this reason, describe its effects hematopoietic stem cells, myoblasts, oligodendrocyte progenitors osteoclast precursors. We also present involvement diseases tissues organs including Alzheimer’s disease, epilepsy, herpes simplex virus type 1 (HSV-1) encephalitis, ischemic stroke, depression, multiple sclerosis, neuromyelitis optica, neuropathic pain, osteoporosis, prion diseases, rheumatoid arthritis, tick-borne encephalitis (TBE), traumatic spinal cord injury West Nile fever.

Language: Английский

Citations

53

Role of HSV-1 in Alzheimer's disease pathogenesis: A challenge for novel preventive/therapeutic strategies DOI Creative Commons
Virginia Protto, Maria Elena Marcocci, Mariya Timotey Miteva

et al.

Current Opinion in Pharmacology, Journal Year: 2022, Volume and Issue: 63, P. 102200 - 102200

Published: March 8, 2022

Herpes simplex virus-1 (HSV-1) is a ubiquitous DNA virus able to establish life-long latent infection in host sensory ganglia. Following periodic reactivations, the neovirions usually target site of primary causing recurrent diseases susceptible individuals. However, reactivated HSV-1 may also reach brain resulting severe herpetic encephalitis or asymptomatic infections. These have been reportedly linked neurodegenerative disorders, such as Alzheimer's disease (AD), suggesting antiviral preventive or/therapeutic treatments possible strategies counteract AD onset and progression. Here, we provide an overview AD-like mechanisms driven by HSV-1-infection neurons discuss ongoing trials repurposing anti-herpetic drugs treat well aimed at blocking infection.

Language: Английский

Citations

46