Mechanisms of Short-Chain Fatty Acids Derived from Gut Microbiota in Alzheimer's Disease

Aging and Disease, Journal Year: 2022, Volume and Issue: 13(4), P. 1252 - 1252

Published: Jan. 1, 2022

Short-chain fatty acids (SCFAs) are important metabolites derived from the gut microbiota through fermentation of dietary fiber. SCFAs participate a number physiological and pathological processes in human body, such as host metabolism, immune regulation, appetite regulation. Recent studies on gut-brain interaction have shown that mediators interactions involved occurrence development many neurodegenerative diseases, including Alzheimer's disease. This review summarizes current research potential roles mechanisms AD. First, we introduce metabolic distribution, specific receptors signaling pathways body. The concentration levels AD patient/animal models then summarized. In addition, illustrate effects cognitive level, features (Aβ tau) neuroinflammation Finally, analyze translational value therapeutic targets for treatment

Language: Английский

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Gut-derived β-amyloid: Likely a centerpiece of the gut–brain axis contributing to Alzheimer’s pathogenesis

Gut Microbes, Journal Year: 2023, Volume and Issue: 15(1)

Published: Jan. 22, 2023

Peripheral β-amyloid (Aβ), including those contained in the gut, may contribute to formation of Aβ plaques brain, and gut microbiota appears exert an impact on Alzheimer's disease (AD) via gut-brain axis, although detailed mechanisms are not clearly defined. The current study focused uncovering potential interactions among gut-derived aging, microbiota, AD pathogenesis. To achieve this goal, expression levels several key proteins involved metabolism were initially assessed mouse with results confirmed human tissue. demonstrated that a high level was detected throughout both mice human, Aβ42 increased age wild type mutant amyloid precursor protein/presenilin 1 (APP/PS1) mice. Next, microbiome characterized by 16S rRNA sequencing, we found altered significantly aged APP/PS1 fecal transplantation (FMT) BACE1 levels. Intra-intestinal injection isotope or fluorescence labeled combined vagotomy also performed investigate transmission from brain. data showed that, mice, transported brain mainly blood rather than vagal nerve. Furthermore, FMT induced neuroinflammation, phenotype mimics early pathology. Taken together, suggests is likely critical source can further upregulate production, thereby potentially contributing

Language: Английский

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Deciphering the Potential Neuroprotective Effects of Luteolin against Aβ1–42-Induced Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(17), P. 9583 - 9583

Published: Sept. 3, 2021

The current study was undertaken to unveil the protective effects of Luteolin, a natural flavonoid, against amyloid-beta (Aβ1-42)-induced neuroinflammation, amyloidogenesis, and synaptic dysfunction in mice. For development an AD mouse model, (Aβ1-42, 5 μL/5 min/mouse) oligomers were injected intracerebroventricularly (i.c.v.) into mice's brain by using stereotaxic frame. After that, mice treated with Luteolin for two weeks at dose 80 mg/kg/day. To monitor biochemical changes, we conducted western blotting immunofluorescence analysis. According our findings, infusion activated c-Jun N-terminal kinases (p-JNK), p38 mitogen-activated protein kinases, glial fibrillary acidic (GFAP), ionized calcium adaptor molecule 1 (Iba-1) cortex hippocampus experimental mice; these changes significantly inhibited Aβ1-42 + Luteolin-treated Likewise, also checked expression inflammatory markers, such as p-nuclear factor-kB p65 (p-NF-kB (Ser536), tissue necrosis factor (TNF-α), Interleukin1-β (IL-1β), Aβ1-42-injected brain, which attenuated brains. Further, investigated pro- anti-apoptotic cell death markers Bax, Bcl-2, Caspase-3, Cox-2, reduced Lut-treated brains compared Aβ-injected group. results indicated that administration Aβ1-42, levels β-site amyloid precursor cleaving enzyme (BACE-1) (Aβ1-42) enhanced, while they We PSD-95 SNAP-25, enhanced underlying factors responsible AD, used specific JNK inhibitor, suggested Aβ-associated neuroinflammation neurodegeneration via inhibition JNK. Collectively, indicate could serve novel therapeutic agent AD-like pathological

Language: Английский

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Therapeutic non-invasive brain treatments in Alzheimer’s disease: recent advances and challenges

Inflammation and Regeneration, Journal Year: 2022, Volume and Issue: 42(1)

Published: Oct. 3, 2022

Abstract Alzheimer’s disease (AD) is one of the major neurodegenerative diseases and most common form dementia. Characterized by loss learning, memory, problem-solving, language, other thinking abilities, AD exerts a detrimental effect on both patients’ families’ quality life. Although there have been significant advances in understanding mechanism underlying pathogenesis progression AD, no cure for AD. The failure numerous molecular targeted pharmacologic clinical trials leads to an emerging research shift toward non-invasive therapies, especially multiple treatments. In this paper, we reviewed widely studied including photobiomodulation (PBM), transcranial magnetic stimulation (TMS), direct current (tDCS), exercise therapy. Firstly, pathological changes challenges studies. We then introduced these therapies discussed factors that may affect effects therapies. Additionally, review possible mechanisms effects. Finally, summarized treatments future studies applications. concluded it would be critical understand exact find optimal treatment parameters improve translational value Moreover, combined use also promising direction sheds light or prevention

Language: Английский

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Autoimmune Neuroinflammatory Diseases: Role of Interleukins

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 7960 - 7960

Published: April 27, 2023

Autoimmune neuroinflammatory diseases are a group of disorders resulting from abnormal immune responses in the nervous system, causing inflammation and tissue damage. The interleukin (IL) family cytokines, especially IL-1, IL-6, IL-17, plays critical role pathogenesis these diseases. IL-1 is involved activation cells, production pro-inflammatory promotion blood-brain barrier breakdown. IL-6 essential for differentiation T cells into Th17 has been implicated initiation progression neuroinflammation. IL-17 potent cytokine produced by that crucial recruiting to sites inflammation. This review summarizes current understanding roles different interleukins autoimmune diseases, including multiple sclerosis, amyotrophic lateral Alzheimer's disease, neuromyelitis optica, encephalitis, discusses potential targeting ILs as therapeutic strategy against We also highlight need further research better understand identify new targets treating debilitating

Language: Английский

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Phytochemicals: A Promising Alternative for the Prevention of Alzheimer’s Disease

Life, Journal Year: 2023, Volume and Issue: 13(4), P. 999 - 999

Published: April 12, 2023

Alzheimer's disease (AD) is a neurological condition that worsens with ageing and affects memory cognitive function. Presently more than 55 million individuals are affected by AD all over the world, it leading cause of death in old age. The main purpose this paper to review phytochemical constituents different plants used for treatment AD. A thorough organized existing literature was conducted, data under sections were found using computerized bibliographic search through use databases such as PubMed, Web Science, Google Scholar, Scopus, CAB Abstracts, MEDLINE, EMBASE, INMEDPLAN, NATTS, numerous other websites. Around 360 papers screened, and, out that, 258 selected on basis keywords relevant information needed be included review. total belonging families have been reported possess bioactive compounds (galantamine, curcumin, silymarin, many more) play significant role These anti-inflammatory, antioxidant, anticholinesterase, anti-amyloid properties safe consumption. This focuses taxonomic details plants, mode action their phytochemicals, safety, future prospects, limitations, sustainability criteria effective

Language: Английский

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Intranasal Drug Delivery by Nanotechnology: Advances in and Challenges for Alzheimer’s Disease Management

Pharmaceutics, Journal Year: 2023, Volume and Issue: 16(1), P. 58 - 58

Published: Dec. 29, 2023

Alzheimer's disease, a progressive neurodegenerative condition, is characterized by gradual decline in cognitive functions. Current treatment approaches primarily involve the administration of medications through oral, parenteral, and transdermal routes, aiming to improve function alleviate symptoms. However, these treatments face limitations, such as low bioavailability inadequate permeation. Alternative invasive methods, while explored, often entail discomfort require specialized assistance. Therefore, development non-invasive efficient delivery system crucial. Intranasal has emerged potential solution, although it constrained unique conditions nasal cavity. An innovative approach involves use nano-carriers based on nanotechnology for intranasal delivery. This strategy overcome current limitations providing enhanced bioavailability, improved permeation, effective traversal blood-brain barrier, extended retention within body, precise targeting brain. The comprehensive review focuses advancements designing various types nano-carriers, including polymeric nanoparticles, metal lipid liposomes, nanoemulsions, Quantum dots, dendrimers. These are specifically tailored therapeutic agents aimed at combatting disease. In summary, utilization systems show significant surmounting constraints disease strategies. Nevertheless, essential acknowledge regulatory well toxicity concerns associated with this route; meticulous consideration required when engineering carrier. underscores revolutionize management highlights importance addressing considerations safe implementations. Embracing could lead substantial field treatment.

Language: Английский

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Corynoxine promotes TFEB/TFE3-mediated autophagy and alleviates Aβ pathology in Alzheimer’s disease models

Acta Pharmacologica Sinica, Journal Year: 2024, Volume and Issue: 45(5), P. 900 - 913

Published: Jan. 15, 2024

Language: Английский

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A nonhuman primate model with Alzheimer’s disease-like pathology induced by hippocampal overexpression of human tau

Alzheimer s Research & Therapy, Journal Year: 2024, Volume and Issue: 16(1)

Published: Jan. 27, 2024

Abstract Background Alzheimer’s disease (AD) is one of the most burdening diseases century with no disease-modifying treatment at this time. Nonhuman primates (NHPs) share genetic, anatomical, and physiological similarities humans, making them ideal model animals for investigating pathogenesis AD potential therapies. However, use NHPs in research has been hindered by paucity monkey models due to their long generation time, ethical considerations, technical challenges genetically modifying monkeys. Methods Here, we developed an AD-like NHP overexpressing human tau bilateral hippocampi adult rhesus macaque We evaluated pathological features these monkeys immunostaining, Nissl staining, cerebrospinal fluid (CSF) analysis, magnetic resonance imaging (MRI), positron emission tomography (PET), behavioural tests. Results demonstrated that after hippocampal overexpression protein, displayed multiple AD, including 3-repeat (3R)/4-repeat (4R) accumulation, hyperphosphorylation, propagation, neuronal loss, atrophy, neuroinflammation, Aβ clearance deficits, blood vessel damage, cognitive decline. More interestingly, accumulation both 3R 4R specific but not found rodents. Conclusions This work establishes a tau-induced many key AD. In addition, our may potentially become adopted researchers worldwide since it can be generated within 2 ~ 3 months through single injection AAVs into brains. Hence, facilitate mechanistic studies therapeutic treatments

Language: Английский

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From basic brain research to treating human brain disorders

Proceedings of the National Academy of Sciences, Journal Year: 2019, Volume and Issue: 116(52), P. 26167 - 26172

Published: Dec. 23, 2019

The human brain is the most complex entity we know. Disorders of are embedded in this complexity. Potential advances treating these disorders result from growing understanding organization. brains monkeys have some important similarities to structure and organization, therefore been extensively studied help us understand disorders. With mind, National Academy Sciences (NAS) convened a colloquium, “Using Monkey Models Understand Develop Treatments for Human Brain Disorders,” Irvine, California on January 7th 8th, 2019. colloquium articles issue PNAS offer glimpse into relationship scientific discovery treatment We begin by considering how kind works. The better know machine works, more likely able fix it when breaks. When our automobile needs repair, take someone think understands works be it. do same thing disorder; go doctor system underlying specific disorder hope that she can provide treatment. It comes first; without hit or miss guess an expensive failure. not all none, continually developing, often over many years. Anyone who has close experience with disease knows current medicine mostly groping dark job basic science turn lights. Consider example contribution clinical … [↵][1]1To whom correspondence may addressed. Email: bob{at}lsr.nei.nih.gov. [1]: #xref-corresp-1-1

Language: Английский

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