Dataset Information

Alleviation of symptoms of Alzheimer's disease by diminishing A? neurotoxicity and neuroinflammation.

ABSTRACT: Alzheimer's disease (AD) is one of the most prevailing neurodegenerative illnesses in the elderly. Accumulation of amyloid-? peptide (A?) and inflammation play critical roles in the pathogenesis and development of AD. Multi-target drugs may interdict the progress of AD through a synergistic mechanism. A neuromodulator, 2-((1H-benzo[d]imidazole-2-yl)methoxy)benzoic acid (BIBA), consisting of an A?-targeting group and a derivative of anti-inflammatory aspirin was designed as a potential anti-AD agent. BIBA exhibits a remarkable inhibitory effect on the self- and metal-induced A? aggregations and shows outstanding anti-inflammatory activity simultaneously. The neurotoxicity of A? aggregates is attenuated, and the production of pro-inflammatory cytokines (PICs), such as IL-6, IL-1? and TNF-?, in microglia stimulated by lipopolysaccharide (LPS) or A? is reduced. Owing to the synergy between the inhibition of A? oligomerization and downregulation of PICs, BIBA markedly prolongs the lifespan and relieves the A?-induced paralysis of A?-transgenic Caenorhabditis elegans, thus showing the potential to ameliorate the symptoms of AD through inhibiting A? neurotoxicity and deactivating microglia. These findings demonstrate that both A? aggregation and neuroinflammation are therapeutic targets for anti-AD drugs, and dual-functional agents that integrate anti-A? and anti-inflammatory capabilities have great advantages over the traditional single-target agents for AD treatment.

SUBMITTER: Yang T

PROVIDER: S-EPMC6979322 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Alleviation of symptoms of Alzheimer's disease by diminishing Aβ neurotoxicity and neuroinflammation.

Yang Tao T Zhu Zhenzhu Z Yin Enmao E Wang Yanqing Y Zhang Changli C Yuan Hao H Zhang Hongmei H Jin Suxing S Guo Zijian Z Wang Xiaoyong X

Chemical science 20190919 43

Alzheimer's disease (AD) is one of the most prevailing neurodegenerative illnesses in the elderly. Accumulation of amyloid-β peptide (Aβ) and inflammation play critical roles in the pathogenesis and development of AD. Multi-target drugs may interdict the progress of AD through a synergistic mechanism. A neuromodulator, 2-((1<i>H</i>-benzo[<i>d</i>]imidazole-2-yl)methoxy)benzoic acid (BIBA), consisting of an Aβ-targeting group and a derivative of anti-inflammatory aspirin was designed as a potent ...[more]

PMID: 32055369

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Project description:Neuroinflammation is a biological process by which the central nervous system responds to stimuli/injuries affecting its homeostasis. So far as this reactive response becomes exacerbated and uncontrolled, it can lead to neurodegeneration, compromising the cognitive and neuropsychiatric domains. Parallelly, modifications in the hypothalamic signaling of neuroprotective hormones linked also to the inflammatory responses of microglia and astrocytes can exacerbate these processes. To complicate the picture, modulations in the gut microbiota (GM) can induce changes in neuroinflammation, altering cognitive and neuropsychiatric functioning. We conducted a web-based search on PubMed. We described studies regarding the cross-talk among microglia and astrocytes in the neuroinflammation processes, along with the role played by the steroid hormones, and how this can reflect on cognitive decline/neurodegeneration, in particular on Alzheimer's Disease (AD) and its neuropsychiatric manifestations. We propose and support the huge literature showing the potentiality of complementary/alternative therapeutic approaches (nutraceuticals) targeting the sustained inflammatory response, the dysregulation of hypothalamic system and the GM composition. NF-κB and Keap1/Nrf2 are the main molecular targets on which a list of nutraceuticals can modulate the altered processes. Since there are some limitations, we propose a new intervention natural treatment in terms of Oxygen-ozone (O2-O3) therapy that could be potentially used for AD pathology. Through a meta-analytic approach, we found a significant modulation of O3 on inflammation-NF-κB/NLRP3 inflammasome/Toll-Like Receptor 4 (TLR4)/Interleukin IL-17α signalling, reducing mRNA (p<0.00001 Odd Ratio (OR)=-5.25 95% CI:-7.04/-3.46) and protein (p<0.00001 OR=-4.85 95%CI:-6.89/-2.81) levels, as well as on Keap1/Nrf2 pathway. Through anti-inflammatory, immune, and steroid hormones modulation and anti-microbial activities, O3 at mild therapeutic concentrations potentiated with nutraceuticals and GM regulators could determine combinatorial effects impacting on cognitive and neurodegenerative domains, neuroinflammation and neuroendocrine signalling, directly or indirectly through the mediation of GM.

Dataset Information

Alleviation of symptoms of Alzheimer's disease by diminishing A? neurotoxicity and neuroinflammation.

Publications

Alleviation of symptoms of Alzheimer's disease by diminishing Aβ neurotoxicity and neuroinflammation.

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