Microglia-mediated T cell infiltration drives neurodegeneration in tauopathy

Nature, Journal Year: 2023, Volume and Issue: 615(7953), P. 668 - 677

Published: March 8, 2023

Language: Английский

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Emerging diagnostics and therapeutics for Alzheimer disease

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(9), P. 2187 - 2199

Published: Sept. 1, 2023

Language: Английский

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Review of Pharmacotherapeutic Targets in Alzheimer’s Disease and Its Management Using Traditional Medicinal Plants

Degenerative Neurological and Neuromuscular Disease, Journal Year: 2024, Volume and Issue: Volume 14, P. 47 - 74

Published: May 1, 2024

Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired daily functioning. While there currently no cure for AD, several pharmacotherapeutic targets management strategies have been explored. Additionally, traditional medicinal plants gained attention their potential role in AD management. Pharmacotherapeutic include amyloid-beta (Aβ) aggregation, tau protein hyperphosphorylation, neuroinflammation, oxidative stress, cholinergic dysfunction. Traditional plants, such as Ginkgo biloba, Huperzia serrata, Curcuma longa (turmeric), Panax ginseng, demonstrated the ability to modulate these through bioactive compounds. biloba , instance, contains flavonoids terpenoids that exhibit neuroprotective effects reducing Aβ deposition enhancing cerebral blood flow. serrata natural source of huperzine A, has acetylcholinesterase-inhibiting properties, thus improving function. enriched with curcumin, exhibits anti-inflammatory antioxidant effects, potentially mitigating neuroinflammation stress. ginseng's ginsenosides shown anti-amyloidogenic properties. The investigation complementary approach offers advantages, including lower risk adverse multi-target interactions. Furthermore, cultural knowledge utilization provide rich information development new therapies. However, further research necessary elucidate precise mechanisms action, standardize preparations, assess safety efficacy remedies. Integrating medicinal-plant-based therapies modern pharmacotherapies may hold key more comprehensive effective treatment. This review aims explore its Keywords: disease, acetylcholinesterase, amyloid beta, protein, medicine, Ayurvedic herbs, acetylcholinesterase inhibitors, disorders, cognition

Language: Английский

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The role of peripheral inflammatory insults in Alzheimer’s disease: a review and research roadmap

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: June 5, 2023

Abstract Peripheral inflammation, defined as inflammation that occurs outside the central nervous system, is an age-related phenomenon has been identified a risk factor for Alzheimer’s disease. While role of chronic peripheral well characterized in context dementia and other conditions, less known about neurologic contribution acute inflammatory insults take place system. Herein, we define immune challenge form pathogen exposure (e.g., viral infection) or tissue damage surgery) causes large, yet time-limited, response. We provide overview clinical translational research examined connection between disease, focusing on three categories have received considerable attention recent years: infection, critical illness, surgery. Additionally, review neurobiological mechanisms which facilitate neural response to discuss potential blood–brain barrier components neuro-immune axis After highlighting knowledge gaps this area research, propose roadmap address methodological challenges, suboptimal study design, paucity transdisciplinary efforts thus far limited our understanding how pathogen- damage-mediated may contribute Finally, therapeutic approaches designed promote resolution be used following preserve brain health limit progression neurodegenerative pathology.

Language: Английский

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Cellular and pathological functions of tau

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(11), P. 845 - 864

Published: July 16, 2024

Language: Английский

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Sodium oligomannate alters gut microbiota, reduces cerebral amyloidosis and reactive microglia in a sex-specific manner

Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)

Published: Feb. 17, 2024

Abstract It has recently become well-established that there is a connection between Alzheimer’s disease pathology and gut microbiome dysbiosis. We have previously demonstrated antibiotic-mediated microbiota perturbations lead to attenuation of Aβ deposition, phosphorylated tau accumulation, disease-associated glial cell phenotypes in sex-dependent manner. In this regard, we were intrigued by the finding marine-derived oligosaccharide, GV-971, was reported alter reduce amyloidosis 5XFAD mouse model treated at point when burden near plateau levels. Utilizing comparable methodologies, but with distinct technical temporal features, now report on impact GV-971 microbiota, microglial APPPS1-21 model, studies performed University Chicago, independently 5X FAD Washington University, St. Louis. Methods To comprehensively characterize effects microbiota-microglia-amyloid axis, conducted two separate investigations independent institutions. There no coordination experimental design or execution laboratories. Indeed, laboratories not aware each other’s experiments until completed. Male female mice daily 40, 80, 160 mg/kg from 8, detectable upto 12 weeks age maximal parallel, corroborate existing published further investigate sex-related differences, male 100 7 9 months peak Subsequently, assessed amyloid-β metagenomic, neuroinflammatory profiles. Finally, initiated Chicago evaluate metabolites cecal tissue vehicle GV-971-treated mice. Results These showed procedural differences (dosage, timing duration treatment) laboratories, cerebral reduced primarily mice, strain. also observed sex-specific following treatment. Interestingly, significantly altered multiple overlapping bacterial species both Moreover, discovered impacted metabolism, particularly elevating amino acid production influencing tryptophan pathway. The metagenomics metabolomics changes correspond notable reductions peripheral pro-inflammatory cytokine chemokine Furthermore, treatment dampened astrocyte microglia activation, decreasing plaque-associated reactive while concurrently increasing homeostatic only Bulk RNAseq analysis unveiled cortex transcriptome profiles, most importantly, group revealed involvement inflammatory responses. Conclusions conclusion, these demonstrate microbiome, neuroinflammation, highlighting potential therapeutic effect GV-971. targets leading lowering plaque signatures manner given onset deposition after already higher

Language: Английский

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Causal relationship between immune cells and neurodegenerative diseases: a two-sample Mendelian randomisation study

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 29, 2024

Background There is increasing evidence that the types of immune cells are associated with various neurodegenerative diseases. However, it currently unclear whether these associations reflect causal relationships. Objective To elucidate relationship between and diseases, we conducted a two-sample Mendelian randomization (MR) analysis. Materials methods The exposure outcome GWAS data used in this study were obtained from an open-access database ( https://gwas.mrcieu.ac.uk/ ), employed MR analysis to assess 731 cell features four including Alzheimer’s disease (AD), Parkinson’s (PD), amyotrophic lateral sclerosis (ALS) multiple (MS). All was Multiple minimize bias obtain reliable estimates variables interest outcomes. Instrumental variable selection criteria restricted ensure accuracy effectiveness species risk Results identified potential relationships different Specifically, found 8 have AD, 1 type has PD, 6 ALS, MS. Conclusion Our study, through genetic means, demonstrates close specific ALS MS, providing useful guidance for future clinical researches.

Language: Английский

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A single-cell and spatial RNA-seq database for Alzheimer’s disease (ssREAD)

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 6, 2024

Abstract Alzheimer’s Disease (AD) pathology has been increasingly explored through single-cell and single-nucleus RNA-sequencing (scRNA-seq & snRNA-seq) spatial transcriptomics (ST). However, the surge in data demands a comprehensive, user-friendly repository. Addressing this, we introduce RNA-seq database for disease (ssREAD). It offers broader spectrum of AD-related datasets, an optimized analytical pipeline, improved usability. The encompasses 1,053 samples (277 integrated datasets) from 67 scRNA-seq snRNA-seq studies, totaling 7,332,202 cells. Additionally, it archives 381 ST datasets 18 human mouse brain studies. Each dataset is annotated with details such as species, gender, region, disease/control status, age, AD Braak stages. ssREAD also provides analysis suite cell clustering, identification differentially expressed spatially variable genes, cell-type-specific marker genes regulons, spot deconvolution integrative analysis. freely available at https://bmblx.bmi.osumc.edu/ssread/ .

Language: Английский

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The advent of Alzheimer treatments will change the trajectory of human aging

Nature Aging, Journal Year: 2024, Volume and Issue: 4(4), P. 453 - 463

Published: April 19, 2024

Language: Английский

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Immunotherapy for depression: Recent insights and future targets

Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 257, P. 108624 - 108624

Published: March 3, 2024

Language: Английский

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