Concurrent suppression of Aβ aggregation and NLRP3 inflammasome activation for treating Alzheimer's disease

Yang, Tao; Zhang, Lei; Shang, Yicun; Jin, Suxing; Guo, Zijian; Wang, Xiaoyong

doi:10.1039/d1sc06071f

Cited by 20 publications

(10 citation statements)

References 62 publications

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“…There is a significant link between NLRP inflammasome and the pathogenesis of Alzheimer’s disease [ 59 , 60 ]. Aβ plaques not only induce oxidative stress and damage neurons, but also activate NLRP3 inflammasomes further releasing IL-1β to trigger neuroinflammation in patients with Alzheimer’s disease [ 61 ]. In neurons, NLRP1 inflammasome levels increase by approximately 25–30 fold in the patients with Alzheimer’s disease [ 62 ].…”

Section: Roles Of Nlrp Inflammasome In Neuropsychiatric Disordersmentioning

confidence: 99%

The Significance of NLRP Inflammasome in Neuropsychiatric Disorders

et al. 2022

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The NLRP inflammasome is a multi-protein complex which mainly consists of the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain. Its activation is linked to microglial-mediated neuroinflammation and partial neuronal degeneration. Many neuropsychiatric illnesses have increased inflammatory responses as both a primary cause and a defining feature. The NLRP inflammasome inhibition delays the progression and alleviates the deteriorating effects of neuroinflammation on several neuropsychiatric disorders. Evidence on the central effects of the NLRP inflammasome potentially provides the scientific base of a promising drug target for the treatment of neuropsychiatric disorders. This review elucidates the classification, composition, and functions of the NLRP inflammasomes. It also explores the underlying mechanisms of NLRP inflammasome activation and its divergent role in neuropsychiatric disorders, including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, depression, drug use disorders, and anxiety. Furthermore, we explore the treatment potential of the NLRP inflammasome inhibitors against these disorders.

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Section: Roles Of Nlrp Inflammasome In Neuropsychiatric Disordersmentioning

confidence: 99%

The Significance of NLRP Inflammasome in Neuropsychiatric Disorders

et al. 2022

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“…AD is crucially related to Aβ plaques, which not only induce oxidative stress but also activate the NLRP3 inflammasome, releasing inflammatory cytokine IL-1β to trigger neuroinflammation. 32 In addition, tau phosphorylation can result in NFT, which is an important histopathological feature of AD. 2 Our previous studies showed that GMs had anti-oxidative, anti-inflammatory and neuroprotective activities, suggesting that GMs could exhibit potential anti-AD effects.…”

Section: Resultsmentioning

confidence: 99%

(±)-Spiroganoapplanin A, a complex polycyclic meroterpenoid dimer from Ganoderma applanatum displaying potential against Alzheimer's disease

Peng

Luo

et al. 2022

Org. Chem. Front.

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“…Benzoic acid derivatives present in garlic shells can be combined with other compounds to synergistically activate the PPAR signaling pathway or inactivate the phospholipase D signaling pathway to exert an anti-T2DM effect ( 86 ). In addition, the bifunctional molecule BPBA synthesized using benzoic acid can target Aβ and inhibit neuroinflammation, which plays a role in AD ( 87 ). To the best of our knowledge, this study is the first to identify the potential role of acetamidobenzoic acid in the pathogenesis of obesity–T2DM–AD, thus laying a foundation for the subsequent development of new drugs.…”

Section: Discussionmentioning

confidence: 99%

High-fiber-diet-related metabolites improve neurodegenerative symptoms in patients with obesity with diabetes mellitus by modulating the hippocampal–hypothalamic endocrine axis

et al. 2023

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ObjectiveThrough transcriptomic and metabolomic analyses, this study examined the role of high-fiber diet in obesity complicated by diabetes and neurodegenerative symptoms.MethodThe expression matrix of high-fiber-diet-related metabolites, blood methylation profile associated with pre-symptomatic dementia in elderly patients with type 2 diabetes mellitus (T2DM), and high-throughput single-cell sequencing data of hippocampal samples from patients with Alzheimer's disease (AD) were retrieved from the Gene Expression Omnibus (GEO) database and through a literature search. Data were analyzed using principal component analysis (PCA) after quality control and data filtering to identify different cell clusters and candidate markers. A protein–protein interaction network was mapped using the STRING database. To further investigate the interaction among high-fiber-diet-related metabolites, methylation-related DEGs related to T2DM, and single-cell marker genes related to AD, AutoDock was used for semi-flexible molecular docking.ResultBased on GEO database data and previous studies, 24 marker genes associated with high-fiber diet, T2DM, and AD were identified. Top 10 core genes include SYNE1, ANK2, SPEG, PDZD2, KALRN, PTPRM, PTPRK, BIN1, DOCK9, and NPNT, and their functions are primarily related to autophagy. According to molecular docking analysis, acetamidobenzoic acid, the most substantially altered metabolic marker associated with a high-fiber diet, had the strongest binding affinity for SPEG.ConclusionBy targeting the SPEG protein in the hippocampus, acetamidobenzoic acid, a metabolite associated with high-fiber diet, may improve diabetic and neurodegenerative diseases in obese people.

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Concurrent suppression of Aβ aggregation and NLRP3 inflammasome activation for treating Alzheimer's disease

Abstract: Bifunctional molecule BPBA inhibits Aβ aggregation and NLRP3 inflammasome activation, thereby decreasing ROS and IL-1β in vitro and vivo; it synergistically prevents Alzheimer's disease via alleviating Aβ neurotoxicity and reducing neuroinflammation.

Cited by 20 publications

References 62 publications

The Significance of NLRP Inflammasome in Neuropsychiatric Disorders

The Significance of NLRP Inflammasome in Neuropsychiatric Disorders

(±)-Spiroganoapplanin A, a complex polycyclic meroterpenoid dimer from Ganoderma applanatum displaying potential against Alzheimer's disease

High-fiber-diet-related metabolites improve neurodegenerative symptoms in patients with obesity with diabetes mellitus by modulating the hippocampal–hypothalamic endocrine axis

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