Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer's disease

Life Sciences, Journal Year: 2020, Volume and Issue: 264, P. 118627 - 118627

Published: Oct. 22, 2020

Language: Английский

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Delivering the power of nanomedicine to patients today

Journal of Controlled Release, Journal Year: 2020, Volume and Issue: 326, P. 164 - 171

Published: July 15, 2020

The situation of the COVID-19 pandemic reminds us that we permanently need high-value flexible solutions to urgent clinical needs including simplified diagnostic technologies suitable for use in field and delivering targeted therapeutics. From our perspective nanotechnology is revealed as a vital resource this, generic platform technical tackle complex medical challenges. It towards this focusing on nanomedicine take issue with Prof Park's recent editorial published Journal Controlled Release. Prof. Park argued last 15 years failed deliver promised innovative patients (Park, K. beginning end hype. Release, 2019; 305, 221-222 [1]. We, ETPN (European Technology Platform Nanomedicine) [2], respectfully disagree. In fact, more than 50 formulations currently market, approval 3 key products (e. g. Onpattro, Hensify Vyxeos), have demonstrated concretely able design overcome critical barriers conventional medicine unique manner, but also within cells new drug-free therapeutic effects by using pure physical modes action, therefore make difference lives. Furthermore, >400 trials are expecting bring novel (e.g. platforms nucleic acid delivery), alone or combination other enabling biotechnologies, microfluidics, advanced materials, biomaterials, smart systems, photonics, robotics, textiles, Big Data ICT (information & communication technologies) generally. However, agree " it time examine sources difficulty translation move forward ". But reaching goal, investments support promising should increase, not decrease. As recently encouraged EMA its roadmap 2025, create unity through common knowledge hub linking academia, industry, healthcare providers hopefully policy makers reduce current fragmentation standardization regulatory body landscape. We promote strategy cross-technology innovation, development high value low-cost solution answer unmet help most projects get better faster clinic. This global vision one chose encourage fifteen years. All actions be taken clear view mind, without any fanfare", focus "on what matters real life", which patient his/her quality life. overview achievements serves reinforce drive further expanding growing maturity healthcare, accelerating pace transformation great potential into tangible breakthroughs.

Language: Английский

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The role of TDP-43 propagation in neurodegenerative diseases: integrating insights from clinical and experimental studies

Experimental & Molecular Medicine, Journal Year: 2020, Volume and Issue: 52(10), P. 1652 - 1662

Published: Oct. 1, 2020

Abstract TAR DNA-binding protein 43 (TDP-43) is a highly conserved nuclear RNA/DNA-binding involved in the regulation of RNA processing. The accumulation TDP-43 aggregates central nervous system common feature many neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer’s disease (AD), and limbic predominant age-related encephalopathy (LATE). Accumulating evidence suggests that prion-like spreading aberrant composed tau, amyloid-β, α-synuclein progression diseases AD PD. Similar to those proteins, pathological can be transferred from cell-to-cell seed-dependent self-templating manner. Here, we review clinical experimental studies supporting misfolded discuss molecular mechanisms underlying propagation these aggregated proteins. idea spreads manner between cells may guide novel therapeutic strategies for TDP-43-associated diseases.

Language: Английский

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The Microbiota–Gut–Brain Axis and Alzheimer’s Disease: Neuroinflammation Is to Blame?

Nutrients, Journal Year: 2020, Volume and Issue: 13(1), P. 37 - 37

Published: Dec. 24, 2020

For years, it has been reported that Alzheimer’s disease (AD) is the most common cause of dementia. Various external and internal factors may contribute to early onset AD. This review highlights a contribution disturbances in microbiota–gut–brain (MGB) axis development Alteration gut microbiota composition determined by increase permeability barrier immune cell activation, leading impairment blood–brain function promotes neuroinflammation, neuronal loss, neural injury, ultimately Numerous studies have shown plays crucial role brain changes behavior individuals formation bacterial amyloids. Lipopolysaccharides amyloids synthesized can trigger cells residing activate response neuroinflammation. Growing experimental clinical data indicate prominent dysbiosis microbiota–host interactions Modulation with antibiotics or probiotic supplementation create new preventive therapeutic options Accumulating evidences affirm research on MGB involvement AD necessary for treatment targets therapies

Language: Английский

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Imaging Techniques in Alzheimer’s Disease: A Review of Applications in Early Diagnosis and Longitudinal Monitoring

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(4), P. 2110 - 2110

Published: Feb. 20, 2021

Background. Alzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting many individuals worldwide with no effective treatment to date. AD characterized by the formation of senile plaques and neurofibrillary tangles, followed neurodegeneration, which leads cognitive decline eventually death. Introduction. In AD, pathological changes occur years before onset. Since disease-modifying therapies may be most beneficial in early stages biomarkers for diagnosis longitudinal monitoring progression are essential. Multiple imaging techniques associated used identify monitor AD. Aim. this review, we discuss contemporary regarding their diagnostic utility, benefits limitations. Additionally, novel techniques, applications research assessed. Findings. Reduced hippocampal volume biomarker but atrophy not an AD-specific measure. Hypometabolism temporoparietal regions seen as However, glucose uptake reflects astrocyte function rather than neuronal function. Amyloid-β (Aβ) earliest hallmark can measured positron emission tomography (PET), Aβ accumulation stagnates progresses. Therefore, suitable progression. The measurement tau PET radiotracers exhibited promising results both monitoring, large-scale validation these required. implementation new processing other contribute understanding finding cure. Conclusions. Several proposed all have limitations specificity, reliability sensitivity. Future perspectives. should focus on expanding employment identifying that reflect pathology stages.

Language: Английский

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Mannan oligosaccharide attenuates cognitive and behavioral disorders in the 5xFAD Alzheimer's disease mouse model via regulating the gut microbiota-brain axis

Brain Behavior and Immunity, Journal Year: 2021, Volume and Issue: 95, P. 330 - 343

Published: April 9, 2021

Language: Английский

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Prospective therapeutic potential of Tanshinone IIA: An updated overview

Pharmacological Research, Journal Year: 2020, Volume and Issue: 164, P. 105364 - 105364

Published: Dec. 4, 2020

Language: Английский

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Towards hospital-on-chip supported by 2D MXenes-based 5th generation intelligent biosensors

Biosensors and Bioelectronics, Journal Year: 2022, Volume and Issue: 220, P. 114847 - 114847

Published: Oct. 27, 2022

Language: Английский

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Microbial-derived metabolites as a risk factor of age-related cognitive decline and dementia

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: June 17, 2022

A consequence of our progressively ageing global population is the increasing prevalence worldwide age-related cognitive decline and dementia. In absence effective therapeutic interventions, identifying risk factors associated with becomes increasingly vital. Novel perspectives suggest that a dynamic bidirectional communication system between gut, its microbiome, central nervous system, commonly referred to as microbiota-gut-brain axis, may be contributing factor for health disease. However, exact mechanisms remain undefined. Microbial-derived metabolites produced in gut can cross intestinal epithelial barrier, enter systemic circulation trigger physiological responses both directly indirectly affecting functions. Dysregulation this (i.e., dysbiosis) modulate cytotoxic metabolite production, promote neuroinflammation negatively impact cognition. review, we explore critical connections microbial-derived (secondary bile acids, trimethylamine-N-oxide (TMAO), tryptophan derivatives others) their influence upon function neurodegenerative disorders, particular interest less-explored role decline.

Language: Английский

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Metformin activates chaperone-mediated autophagy and improves disease pathologies in an Alzheimer disease mouse model

Protein & Cell, Journal Year: 2021, Volume and Issue: 12(10), P. 769 - 787

Published: July 21, 2021

Chaperone-mediated autophagy (CMA) is a lysosome-dependent selective degradation pathway implicated in the pathogenesis of cancer and neurodegenerative diseases. However, mechanisms that regulate CMA are not fully understood. Here, using unbiased drug screening approaches, we discover Metformin, commonly first medication prescribed for type 2 diabetes, can induce CMA. We delineate mechanism induction by Metformin to be via activation TAK1-IKKα/β signaling leads phosphorylation Ser85 key mediator CMA, Hsc70, its activation. Notably, find amyloid-beta precursor protein (APP) substrate it binds Hsc70 an IKKα/β-dependent manner. The inhibition CMA-mediated APP enhances cytotoxicity. Importantly, APP/PS1 mouse model Alzheimer's disease (AD), overexpression or potently reduces accumulated brain Aβ plaque levels reverses molecular behavioral AD phenotypes. Our study elucidates novel regulation Metformin-TAK1-IKKα/β-Hsc70 suggests as new activator diseases, such AD, where therapeutic intervention could beneficial.

Language: Английский

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