An in-silico approach: identification of PPAR-γ agonists from seaweeds for the management of Alzheimer’s Disease

Kotha, Satvik; Swapna, B; Kulkarni, Vithal M.; Setty, Sreenivasa; Kumar, Bhupinder; Harisha, Rajappa

doi:10.1080/07391102.2020.1747543

Cited by 13 publications

(22 citation statements)

References 46 publications

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“…LPL is a downstream target gene of lipid-activated transcription factor PPARγ, which has been reported to be implicated in the progression of AD (Medrano-Jiménez et al, 2019;Chamberlain et al, 2020;Kotha et al, 2020;Xie et al, 2020). This study demonstrated that the expression of PPARγ was decreased in SHSY5Y cells exposed to 2 µM Aβ, and increased in cells with 10 µM Aβ exposure.…”

Section: Discussionmentioning

confidence: 53%

“…The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated transcription factor, forms heterodimers with retinoid X receptors and recognizes specific DNA sequences called PPAR response elements in LPL gene, thereby up-regulating the expression of LPL (Goto, 2019;Kotha et al, 2020). Silencing HDAC2 causes a down-regulation of PPARγ expression in Bone marrow mesenchymal stem cells (Lee et al, 2014), whereas inhibiting HDAC3 results in an up-regulation PPARγ expression in mouse embryonic fibroblast cells or Human embryonic kidney cells (Jiang et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Exploration of the Molecular Mechanism for Lipoprotein Lipase Expression Variations in SH-SY5Y Cells Exposed to Different Doses of Amyloid-Beta Protein

Zhang

Liu

Wang

et al. 2020

Front. Aging Neurosci.

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Progressive accumulation of amyloid-β (Aβ) plaques in the brain is a characteristic pathological change in Alzheimer's disease (AD). We previously found the expression of lipoprotein lipase (LPL) was increased in SH-SY5Y cells exposed to low-dose Aβ and decreased in cells with high-dose Aβ exposure, but the molecular mechanism is still unclear. Based on previous studies, the opposite regulation of histone deacetylase2 (HDAC2) and HDAC3 on LPL expression probably explain the above molecular mechanism, in which microRNA-29a and peroxisome proliferator-activated receptor γ (PPARγ) may be involved. This study further revealed the mechanism of HDAC2 and HDAC3 on conversely regulating LPL expression. The results showed that HDAC2 down-regulated microRNA-29a by decreasing histone acetylation (Ace-H3K9) level in its promoter region, subsequently increasing LPL expression directly or through PPARγ/LPL pathway; HDAC3 decreased LPL expression through inhibiting Ace-H3K9 levels in LPL and PPARγ promoter regions and up-regulating microRNA-29a. This study also found that with increasing concentrations of Aβ in cells, HDAC2 and HDAC3 expression were gradually increased, and Ace-H3K9 levels in LPL and PPARγ promoter region regulated by HDAC3 were decreased correspondingly, while Ace-H3K9 levels in microRNA-29a promoter region modulated by HDAC2 were not decreased gradually but presented a U-shaped trend. These may lead to the results that a U-shaped alteration in microRNA-29a expression, subsequently leading to an inverse U-shaped alteration in PPARγ or LPL expression. In conclusion, HDAC2 and HDAC3 at least partly mediate LPL expression variations in different concentrations of Aβ exposed SH-SY5Y cells, in which microRNA-29a and PPARγ are involved, and the histone acetylation level in microRNA-29a promoter region plays a key role.

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Section: Discussionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Exploration of the Molecular Mechanism for Lipoprotein Lipase Expression Variations in SH-SY5Y Cells Exposed to Different Doses of Amyloid-Beta Protein

Zhang

Liu

Wang

et al. 2020

Front. Aging Neurosci.

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“…In another instance, we had investigated the synthesis of furan and pyran containing cage systems using RCM protocol. [31] In this regard, we have used cage diones 94, 95, and 96 bearing spiro ring system for the preparation of variety of oxa-cage compounds contain tetrahydrofuran and pyran ring. These cage compounds 94-96 were synthesized by employing DA reaction of 1,4-benzoquinone 93 with 31, 32, and 33 (dienes) followed by [2 + 2] cycloaddition (Scheme 12).…”

Section: Chemcatchemmentioning

confidence: 99%

“…Additionally, we synthesized the tetrahydrofuran ring containing cage compounds via vinyl Grignard addition. [31] Here, the diones 94, 95, and 96 were subjected to vinyl Grignard appropriate diene partners 31, 32, and 33 followed by [2 + 2] cycloaddition reaction (Scheme 16).…”

Section: Chemcatchemmentioning

confidence: 99%

“…We have also assembled various oxa cage derivatives starting with cage diones involving acid-catalyzed acetalization with the aid of allyl alcohol and 2,2'-dimethoxy propane (Scheme 19). [37] The requisite Cookson type diones were produced from easily available sources such as 1,3-cyclopentadiene (31), spirodienes (32 & 33), and p-benzoquinone derivatives through a DA reaction and [2 + 2] photocycloaddition as key steps. The cage diketone 139 (R 1 = H; n = 0) was treated with allyl alcohol and 2,2'-dimethoxy propane in the presence of catalytic p-TsOH to produce the oxo-ketal 141 a along with an inseparable mixture of diastereomers 142 a and 143 a (1 : 0 : 8).…”

Section: Synthesis Of Oxa-cage Framework Via Acetalizationmentioning

confidence: 99%

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Design and Synthesis of Cage Molecules as High Energy Density Materials for Aerospace Applications

2020

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This account deals with our work on cage systems that was reported during the past two decades. Here, we summarized various new synthetic routes to diverse cage polycycles by employing Claisen rearrangement, Diels−Alder (DA) reaction, [2+2] photocycloaddition, Grignard addition, Fischer indolization, ring‐closing metathesis (RCM), Van Leusen oxazole synthesis, and rearrangement reaction as key steps. Several heterocyclic cage frameworks (oxacycles and oxazoles), polycyclic bisindoles, cage spirocycles, cage energetic systems, D3‐trishomocubanes, cage propellanes and unusual polycycles were designed starting with inexpensive and easily accessible starting materials. In some occasions, we also prepared biologically important triquinane frameworks starting with readily available cage diones via photo‐thermal olefin metathesis strategy under microwave irradiation conditions. This new protocol avoids specialized equipment such as flash vacuum pyrolysis. Additionally, we have also shown interesting rearrangements in cage frameworks to generate unusual new and cage systems with the aid of the Lewis acids such as BF3.OEt2. Moreover, these functionalized cage systems can be considered as a useful candidates in material science, medicinal chemistry, and also in drug in design.

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Discovery of VEGFR-2 inhibitors exerting significant anticancer activity against CD44+ and CD133+ cancer stem cells (CSCs): Reversal of TGF-β induced epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma

Modi

Kulkarni

2020

European Journal of Medicinal Chemistry

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An in-silico approach: identification of PPAR-γ agonists from seaweeds for the management of Alzheimer’s Disease

Cited by 13 publications

References 46 publications

Exploration of the Molecular Mechanism for Lipoprotein Lipase Expression Variations in SH-SY5Y Cells Exposed to Different Doses of Amyloid-Beta Protein

Exploration of the Molecular Mechanism for Lipoprotein Lipase Expression Variations in SH-SY5Y Cells Exposed to Different Doses of Amyloid-Beta Protein

Design and Synthesis of Cage Molecules as High Energy Density Materials for Aerospace Applications

Discovery of VEGFR-2 inhibitors exerting significant anticancer activity against CD44+ and CD133+ cancer stem cells (CSCs): Reversal of TGF-β induced epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma

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