Phytomedicine, Journal Year: 2023, Volume and Issue: 120, P. 155020 - 155020
Published: Aug. 17, 2023
Language: Английский
Neuron, Journal Year: 2023, Volume and Issue: 111(7), P. 1086 - 1093.e2
Published: Jan. 19, 2023
Language: Английский
Citations
212
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
Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 22(7), P. 444 - 458
Published: Nov. 11, 2021
Language: Английский
Citations
115
Neuropharmacology, Journal Year: 2022, Volume and Issue: 209, P. 109023 - 109023
Published: March 4, 2022
Language: Английский
Citations
80
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
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
Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)
Published: Sept. 4, 2024
Language: Английский
Citations
19
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
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
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