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Pharmacoinformatic and molecular docking studies reveal potential novel antidepressants against neurodegenerative disorders by targeting HSPB8.

ABSTRACT: Charcot-Marie-Tooth (CMT) disease is an inherited peripheral neuromuscular disorder characterized by length-dependent and progressive degeneration of peripheral nerves, leading to muscular weakness. Research has shown that mutated HSPB8 may be responsible for depression, neurodegenerative disorders, and improper functioning of peripheral nerves, resulting in neuromuscular disorders like CMT. In the current work, a hybrid approach of virtual screening and molecular docking studies was followed by homology modeling and pharmacophore identification. Detailed screening analyses were carried out by 2-D similarity search against prescribed antidepressant drugs with physicochemical properties. LigandScout was employed to ascertain novel molecules and pharmacophore properties. In this study, we report three novel compounds that showed maximum binding affinity with HSPB8. Docking analysis elucidated that Met37, Ser57, Ser58, Trp60, Thr63, Thr114, Lys115, Asp116, Gly117, Val152, Val154, Leu186, Asp189, Ser190, Gln191, and Glu192 are critical residues for ligand-receptor interactions. Our analyses suggested paroxetine as a potent compound for targeting HSPB8. Selected compounds have more effective energy scores than the selected drug analogs. Additionally, site-directed mutagenesis could be significant for further analysis of the binding pocket. The novel findings based on an in silico approach may be momentous for potent drug design against depression and CMT.

SUBMITTER: Sehgal SA

PROVIDER: S-EPMC4866741 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Pharmacoinformatic and molecular docking studies reveal potential novel antidepressants against neurodegenerative disorders by targeting HSPB8.

Sehgal Sheikh Arslan SA Mannan Shazia S Ali Sannia S

Drug design, development and therapy 20160506

Charcot-Marie-Tooth (CMT) disease is an inherited peripheral neuromuscular disorder characterized by length-dependent and progressive degeneration of peripheral nerves, leading to muscular weakness. Research has shown that mutated HSPB8 may be responsible for depression, neurodegenerative disorders, and improper functioning of peripheral nerves, resulting in neuromuscular disorders like CMT. In the current work, a hybrid approach of virtual screening and molecular docking studies was followed by ...[more]

PMID: 27226709

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Project description:Diet has been hypothesized to be associated with neurodegenerative disorders. The aim was to conduct an umbrella review to summarize and evaluate the current evidence of prospective associations between any dietary factors and the incidence of neurodegenerative disorders. We conducted a systematic search in PubMed, Embase, and the Cochrane library up to November 2019 to identify systematic reviews with meta-analyses of prospective studies investigating the association between dietary factors (dietary patterns, foods and beverages, nutrients, and phytochemicals) and neurodegenerative disorders (cognitive decline, cognitive impairment, Alzheimer disease, all-cause dementia, and Parkinson disease). Summary risk ratios (SRRs) and 95% CIs were recalculated using a random effects model. We evaluated the risk of bias of identified meta-analyses and the quality of evidence for all associations. In total, 20 meta-analyses including 98 SRRs were identified. All original meta-analyses were rated as being at high risk of bias. Methodological concerns related mainly to the inappropriate synthesis, assessment, and discussion of the risk of bias of primary studies. For the recalculated meta-analyses, quality of evidence was moderate for inverse associations between higher adherence to the Mediterranean diet (SRR: 0.63; 95% CI: 0.48, 0.82; n = 4 primary studies) and higher fish intake (SRR: 0.72; 95% CI: 0.59, 0.89; n = 6) and Alzheimer disease, as well as for tea consumption and all-cause dementia (SRR: 0.74; 95% CI: 0.63, 0.88; n = 2) and Parkinson disease (SRR per 2 cups/d: 0.69; 95% CI: 0.54, 0.87; n = 5). This umbrella review provides a comprehensive overview of the available evidence on dietary factors and neurodegenerative disorders. The results indicate that the Mediterranean diet, fish, and tea could be inversely associated with neurodegenerative disorders. However, the quality of evidence was generally low, suggesting that further studies are likely to change the overall estimates. Thus, more well-conducted research, also investigating other dietary factors in association with neurodegenerative disorders, is warranted.

Dataset Information

Pharmacoinformatic and molecular docking studies reveal potential novel antidepressants against neurodegenerative disorders by targeting HSPB8.

Publications

Pharmacoinformatic and molecular docking studies reveal potential novel antidepressants against neurodegenerative disorders by targeting HSPB8.

Similar Datasets

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