Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease

Science Translational Medicine, Journal Year: 2016, Volume and Issue: 8(340)

Published: May 25, 2016

β-Amyloid protein oligomerization and fibrillization, known to be pathogenic in Alzheimer’s disease, may play a physiological role microbial entrapment innate immunity.

Language: Английский

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Alzheimer’s Disease-Associated β-Amyloid Is Rapidly Seeded by Herpesviridae to Protect against Brain Infection

Neuron, Journal Year: 2018, Volume and Issue: 99(1), P. 56 - 63.e3

Published: July 1, 2018

Language: Английский

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Microbes and Alzheimer’s Disease

Journal of Alzheimer s Disease, Journal Year: 2016, Volume and Issue: 51(4), P. 979 - 984

Published: April 12, 2016

We are researchers and clinicians working on Alzheimer’s disease (AD) or related topics, we write to express our concern that one particular aspect of the has been neglected, even thoug ...

Language: Английский

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Amyloid β-based therapy for Alzheimer’s disease: challenges, successes and future

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: June 30, 2023

Abstract Amyloid β protein (Aβ) is the main component of neuritic plaques in Alzheimer’s disease (AD), and its accumulation has been considered as molecular driver pathogenesis progression. Aβ prime target for development AD therapy. However, repeated failures Aβ-targeted clinical trials have cast considerable doubt on amyloid cascade hypothesis whether drug followed correct course. recent successes targeted assuaged those doubts. In this review, we discussed evolution over last 30 years summarized application diagnosis modification. particular, extensively pitfalls, promises important unanswered questions regarding current anti-Aβ therapy, well strategies further study more feasible approaches optimization prevention treatment.

Language: Английский

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The antimicrobial protection hypothesis of Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2018, Volume and Issue: 14(12), P. 1602 - 1614

Published: Oct. 9, 2018

Abstract Objective We explore here a novel model for amyloidogenesis in Alzheimer's disease (AD). This new perspective on AD amyloidosis seeks to provide rational framework incorporating recent and seemingly independent findings the antimicrobial role of β‐amyloid emerging experimental, genetic, epidemiological data, suggesting innate immune‐mediated inflammation propagates neurodegeneration. Background pathology is characterized by cerebral deposition amyloid‐β protein (Aβ) as β‐amyloid. Genetic studies have confirmed key Aβ AD, revealing that mutation‐mediated shifts peptides generation lead early onset familial disease. However, appears normal majority patients, who lack mutations. In prevailing models nonfamilial individual genetics age‐associated changes brain milieu promote an intrinsically abnormal propensity self‐association. are increasingly inconsistent with characterization oligomerization nonphysiological exclusively pathological activity. Recent suggest ancient, highly conserved effector molecule immunity. Moreover, appear be important immune pathways mediate pathogen entrapment protect against infection. New inflammation‐mediated neurodegeneration immunity led emergence “Antimicrobial Protection Hypothesis” AD. this model, response genuine, or mistakenly perceived, immunochallenge. first entraps neutralizes invading pathogens fibrillization drives neuroinflammatory help fight infection clear β‐amyloid/pathogen deposits. chronic activation pathway leads sustained Mounting data link elevated microbe levels The Antimicrobial Hypothesis reveals how increased microbial burden may directly exacerbate deposition, inflammation, progression. Amyloid cascade hypothesis protection modality Aβ's pathophysiology shifted from stochastic behavior toward dysregulated response. still Thus, extends but remains broadly consistent Cascade overwhelming showing primacy pathology.

Language: Английский

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Self-assembling dipeptide antibacterial nanostructures with membrane disrupting activity

Nature Communications, Journal Year: 2017, Volume and Issue: 8(1)

Published: Nov. 3, 2017

Abstract Peptide-based supramolecular assemblies are a promising class of nanomaterials with important biomedical applications, specifically in drug delivery and tissue regeneration. However, the intrinsic antibacterial capabilities these have been largely overlooked. The recent identification common characteristics shared by self-assembling peptides provides paradigm shift towards development agents. Here we present activity self-assembled diphenylalanine, which emerges as minimal model for polymers. diphenylalanine nano-assemblies completely inhibit bacterial growth, trigger upregulation stress-response regulons, induce substantial disruption to morphology, cause membrane permeation depolarization. We demonstrate specificity interactions materials integration peptide into scaffolds. This study insights significance interplay between self-assembly antimicrobial establishes innovative design principles toward agents materials.

Language: Английский

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The role of astrocytes in amyloid production and Alzheimer's disease

Open Biology, Journal Year: 2017, Volume and Issue: 7(12), P. 170228 - 170228

Published: Dec. 1, 2017

Alzheimer's disease (AD) is marked by the presence of extracellular amyloid beta (Aβ) plaques, intracellular neurofibrillary tangles (NFTs) and gliosis, activated glial cells, in brain. It thought that Aβ plaques trigger NFT formation, neuronal cell death, neuroinflammation gliosis and, ultimately, cognitive impairment. There are increased numbers reactive astrocytes AD, which surround secrete proinflammatory factors can phagocytize break down Aβ. was cells were major source However, mounting evidence suggests may play an additional role AD secreting significant quantities contributing to overall burden Astrocytes most numerous type brain, therefore even minor secretion from individual could prove be substantial when taken across whole Reactive have levels three necessary components for production: precursor protein, β-secretase (BACE1) γ-secretase. The identification environmental factors, such as neuroinflammation, promote astrocytic production, redefine how we think about developing therapeutics AD.

Language: Английский

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The Infectious Etiology of Alzheimer’s Disease

Current Neuropharmacology, Journal Year: 2017, Volume and Issue: 15(7)

Published: March 15, 2017

Inflammation is a part of the first line defense body against invasive pathogens, and plays crucial role in tissue regeneration repair. A proper inflammatory response ensures suitable resolution inflammation elimination harmful stimuli, but when reactions are inappropriate it can lead to damage surrounding normal cells. The relationship between infections Alzheimer's Disease (AD) etiology, especially lateonset AD (LOAD) has been continuously debated over past three decades.This review discusses whether could be causative factor that promotes progression summarizes recent investigations associating infectious agents chronic with AD. Preventive therapeutic approaches context an etiology disease also discussed.Emerging evidence supports hypothesis neurotropic viruses from Herpesviridae family, Human herpesvirus 1 (HHV-1), Cytomegalovirus (CMV), 2 (HHV-2), neuropathology. Recent indicate association Hepatitis C virus (HCV) infection dementia. Among bacteria special attention focused on spirochetes family periodontal pathogens such as Porphyromonas gingivalis or Treponema denticola cause periodontitis possibly contribute clinical onset AD.Chronic viral, bacterial fungal might factors for pathway

Language: Английский

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The Physiological Roles of Amyloid-β Peptide Hint at New Ways to Treat Alzheimer's Disease

Frontiers in Aging Neuroscience, Journal Year: 2018, Volume and Issue: 10

Published: April 25, 2018

Amyloid-ß (Aß) is best known as the misfolded peptide that involved in pathogenesis of Alzheimer's disease (AD), and it currently primary therapeutic target attempts to arrest course this disease. This notoriety has overshadowed evidence Aß serves several important physiological functions. present throughout lifespan, been found all vertebrates examined thus far, its molecular sequence shows a high degree conservation. These features are typical factor contributes significantly biological fitness, suggestion supported by functions beneficial for brain. The putative roles include protecting body from infections, repairing leaks blood-brain barrier, promoting recovery injury, regulating synaptic function. Evidence these comes vitro vivo studies, which have shown cellular production rapidly increases response challenge often diminishes upon recovery. further adverse outcomes clinical trials attempted deplete order treat AD. We suggest anti-Aß therapies will produce fewer effects if triggers deposition (e.g. pathogens, hypertension diabetes) addressed first.

Language: Английский

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Periodontal disease associates with higher brain amyloid load in normal elderly

Neurobiology of Aging, Journal Year: 2014, Volume and Issue: 36(2), P. 627 - 633

Published: Nov. 5, 2014

Language: Английский

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