Aβ42 Expressing <i>Drosophila melanogaster</i> Model for Alzheimer's Disease: Quantitative Proteomics Identifies Altered Protein Dynamics of Relevance to Neurodegeneration

Deolankar, Sayali Chandrashekhar; Najar, Mohammad Altaf; Raghu, Shamprasad Varija; Prasad, T. S. Keshava

doi:10.1089/omi.2021.0173

Cited by 4 publications

(2 citation statements)

References 62 publications

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“…Research is ongoing for the Aβ-protein hypothesis, and particularly for Aβ 42 . 35,36 Our results contribute potential leads for antiaggregation research on Alzheimer's disease.…”

Section: Journal Of Natural Productsmentioning

confidence: 74%

Anti-Aβ42 Aggregative Polyketides from the Antarctic Psychrophilic Fungus Pseudogymnoascus sp. OUCMDZ-3578

et al. 2023

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Seven new polyketides, diphenyl ketone (1), diphenyl ketone glycosides (2−4), diphenyl ketone-diphenyl ether dimer (6), and anthraquinone-diphenyl ketone dimers (7 and 8), together with compound 5, were isolated from the psychrophilic fungus Pseudogymnoascus sp. OUCMDZ-3578 fermented at 16 °C and identified by spectroscopic analysis. The absolute configurations of 2−4 were determined by acid hydrolysis and 1-phenyl-3-methyl-5-pyrazolone precolumn derivatization. The configuration of 5 was first determined by X-ray diffraction analysis. Compounds 6 and 8 showed the highest activity against amyloid beta (Aβ 42 ) aggregation with half-maximal inhibitory concentrations (IC 50 ) of 0.10 and 0.18 μM, respectively. They also showed strong abilities to chelate with metal ions, especially iron, were sensitive to Aβ 42 aggregation induced by metal ions, and displayed depolymerizing activity. Compounds 6 and 8 show potential as leads for the treatment of Alzheimer's disease to prevent Aβ 42 aggregation.

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“…Research is ongoing for the Aβ-protein hypothesis, and particularly for Aβ 42 . 35,36 Our results contribute potential leads for antiaggregation research on Alzheimer's disease.…”

Section: Journal Of Natural Productsmentioning

confidence: 74%

Anti-Aβ42 Aggregative Polyketides from the Antarctic Psychrophilic Fungus Pseudogymnoascus sp. OUCMDZ-3578

et al. 2023

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“…Differential expression analysis in THICAPA-treated Drosophila has shown that Imd and Toll pathways, which are essential in innate immunity against infections and inflammations, were downregulated [ 85 ]. Drosophila expressing human Aβ42 in photoreceptor cells showed that the Toll pathway was involved in Aβ42-induced neurotoxicity [ 86 ]. In contrast, it was claimed that the clumping of Aβ42 was able to protect against microbes and trigger harmful inflammation in the central nervous system [ 87 ].…”

Section: Tetrahydroisoquinoline Derivativesmentioning

confidence: 99%

A comprehensive review on the progress and challenges of tetrahydroisoquinoline derivatives as a promising therapeutic agent to treat Alzheimer's disease

Thangeswaran,

Shamsuddin,

Balakrishnan

2024

Heliyon

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Discovery of Molecular Networks of Neuroprotection Conferred by Brahmi Extract in Aβ42-Induced Toxicity Model of Drosophila melanogaster Using a Quantitative Proteomic Approach

et al. 2022

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Accumulation of Aβ 42 peptides forming plaque in various regions of the brain is a hallmark of Alzheimer's disease (AD) progression. However, to date, there is no effective management strategy reported for attenuation of Aβ 42 induced toxicity in the early stages of the disease. Alternate medicinal systems such as Ayurveda in the past few decades show promising results in the management of neuronal complications. Medhya Rasayana such as Brahmi is known for its neuroprotective properties via resolving memory-related issues, while the underlying molecular mechanism of the same remains unclear. In the present study, we aimed to understand the neuroprotective effects of the aqueous extract of Bacopa monnieri and Centella asiatica (commonly known as Brahmi) against the Aβ 42 expressing model of the Drosophila melanogaster. By applying a quantitative proteomics approach, the study identi ed > 90% of differentially expressed proteins from Aβ 42 expressing D. melanogaster were either restored to their original expression pattern or showed no change in expression pattern upon receiving either Brahmi extract treatment. The Brahmi restored proteins were part of neuronal pathways associated with cell cycle re-entry, apoptosis, and mitochondrial dynamics. The neuroprotective effect of Brahmi was also validated by negative geotaxis behavioral analysis suggesting its protective role against behavioral de cits exerted by Aβ 42 toxicity. We believe that these discoveries will provide a platform for developing novel therapeutics for AD management by deciphering molecular targets of neuroprotection conferred by an aqueous extract of Bacopa monnieri or Centella asiatica.

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Aβ42 Expressing Drosophila melanogaster Model for Alzheimer's Disease: Quantitative Proteomics Identifies Altered Protein Dynamics of Relevance to Neurodegeneration

Cited by 4 publications

References 62 publications

Anti-Aβ42 Aggregative Polyketides from the Antarctic Psychrophilic Fungus Pseudogymnoascus sp. OUCMDZ-3578

Anti-Aβ42 Aggregative Polyketides from the Antarctic Psychrophilic Fungus Pseudogymnoascus sp. OUCMDZ-3578

A comprehensive review on the progress and challenges of tetrahydroisoquinoline derivatives as a promising therapeutic agent to treat Alzheimer's disease

Discovery of Molecular Networks of Neuroprotection Conferred by Brahmi Extract in Aβ42-Induced Toxicity Model of Drosophila melanogaster Using a Quantitative Proteomic Approach

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