Inhibiting amyloid-β cytotoxicity through its interaction with the cell surface receptor LilrB2 by structure-based design

Cao, Qing; Shin, Woo Shik; Chan, Henry; Vuong, Celine K.; Dubois, Bethany; Li, Binsen; Murray, Kevin; Sawaya, M.R.; Feigon, Juli; Black, Douglas L.; Eisenberg, David; Jiang, Lin

doi:10.1038/s41557-018-0147-z

Cited by 56 publications

(63 citation statements)

References 45 publications

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“…Therefore, binding between oAβ and PirB would recruit cofilin-signaling modules, which leads to actin depolymerization, resulting in synaptic dysfunction and cognitive deficits [93]. Compounds inhibiting Aβ/LilrB2 interactions in vitro have been identified, and potentially bioactive Aβ/LilrB2 inhibitors such as ALI6 can inhibit Aβ-mediated neurotoxicity in primary neurons [94].…”

Section: Lilrb2mentioning

confidence: 99%

Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease

Guo

Zhang

Zeng

et al. 2020

Mol Neurodegeneration

621

365

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Alzheimer's disease (AD) is the most common neurodegenerative disorder seen in age-dependent dementia. There is currently no effective treatment for AD, which may be attributed in part to lack of a clear underlying mechanism. Studies within the last few decades provide growing evidence for a central role of amyloid β (Aβ) and tau, as well as glial contributions to various molecular and cellular pathways in AD pathogenesis. Herein, we review recent progress with respect to Aβ-and tau-associated mechanisms, and discuss glial dysfunction in AD with emphasis on neuronal and glial receptors that mediate Aβ-induced toxicity. We also discuss other critical factors that may affect AD pathogenesis, including genetics, aging, variables related to environment, lifestyle habits, and describe the potential role of apolipoprotein E (APOE), viral and bacterial infection, sleep, and microbiota. Although we have gained much towards understanding various aspects underlying this devastating neurodegenerative disorder, greater commitment towards research in molecular mechanism, diagnostics and treatment will be needed in future AD research.

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Section: Lilrb2mentioning

confidence: 99%

Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease

Guo

Zhang

Zeng

et al. 2020

Mol Neurodegeneration

621

365

View full text Add to dashboard Cite

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“…The binding ability, sites, and interactions between compound and target proteins were achieved and analyzed by classical molecular dynamics using AutoDockTools-1.5.6, Pymol 2.3 and Discovery Studio 4.5 Client [77,78]. The 3D chemical structural formulas of candidate compounds were obtained from PubChem and energy minimizing employed to ChemBioDraw 3D.…”

Section: Molecular Dockingmentioning

confidence: 99%

Pharmacological Mechanisms Underlying the Neuroprotective Effects of Alpinia oxyphylla Miq. on Alzheimer’s Disease

Wang

Guo

et al. 2020

IJMS

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Alpinia oxyphylla Miq. (i.e., A. oxyphylla), a traditional Chinese medicine, can exert neuroprotective effects in ameliorating mild cognitive impairment and improving the pathological hallmarks of Alzheimer's disease (AD). Here, 50 active compounds and 164 putative targets were collected and identified with 251 clinically tested AD-associated target proteins using network pharmacology approaches. Based on the Gene Ontology/Kyoto Encyclopedia of Genes and Genomes pathway enrichments, the compound-target-pathway-disease/protein-protein interaction network constructions, and the network topological analysis, we concluded that A. oxyphylla may have neuroprotective effects by regulating neurotransmitter function, as well as brain plasticity in neuronal networks. Moreover, closely-related AD proteins, including the amyloid-beta precursor protein, the estrogen receptor 1, acetylcholinesterase, and nitric oxide synthase 2, were selected as the bottleneck nodes of network for further verification by molecular docking. Our analytical results demonstrated that terpene, as the main compound of A. oxyphylla extract, exerts neuroprotective effects, providing new insights into the development of a natural therapy for the prevention and treatment of AD.

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“…Therefore the LilrB2 binding moieties of Aβ with identified structure, be 16 KLVFFA 21 , has been used to inhibit this interaction and its efficacy has been studied in vivo and in vitro. This study showed that these inhibitors are potential therapeutic agents against AD (Cao et al, 2018).…”

Section: Alzheimer's Disease Treatment With Small Molecule β-Amyloid mentioning

confidence: 66%

The recent development in synthesis and pharmacological evaluation of small molecule to treat Alzheimer's diseases: A review

2020

Int. J. Adv. Biol. Biomed. Res.

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Alzheimer's disease is a neurological disorder in which the death of brain cells causes memory loss and cognitive decline. It is a neurodegenerative type of dementia, the disease starts mild and gets progressively worse. Like all types of dementia, Alzheimer's is caused by brain cell death. The most common presentation marking Alzheimer's dementia is where symptoms of memory loss are the most prominent, especially in the area of learning and recalling new information. Alzheimer's disease is not simple to diagnose for which there is no single test. For this reason, the first thing doctors do is to rule out other problems before confirming whether mental signs and symptoms are severe enough to be a kind of dementia or something else. Genetic test is possible in some settings to indicate the likelihood of someone having or developing the disease but this is controversial and not entirely reliable. There are no disease-modifying drugs available for Alzheimer's disease but some options may reduce its symptoms and help improve quality of life. A different kind of drug, namely memantine, an NMDA receptor antagonist, may also be used, alone or in combination with a cholinesterase inhibitor. This review highlights the several reports that attempt to design and synthesis of some classes of selective Alzheimer's disease inhibitors.

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Inhibiting amyloid-β cytotoxicity through its interaction with the cell surface receptor LilrB2 by structure-based design

Cited by 56 publications

References 45 publications

Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease

Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease

Pharmacological Mechanisms Underlying the Neuroprotective Effects of Alpinia oxyphylla Miq. on Alzheimer’s Disease

The recent development in synthesis and pharmacological evaluation of small molecule to treat Alzheimer's diseases: A review

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