Differential gene expression by RNA-seq during Alzheimer’s disease-like progression in the Drosophila melanogaster model

Silva, Jéssica Regina da Costa; Fujimura, Patrícia Tiemi; Batista, Letícia Leandro; Malta, Serena Mares; Filho, Romualdo Morandi; Silva, Matheus Henrique; Souza, Aline Gomes de; Mendes‐Silva, Ana Paula; Borges, Luiza Diniz Ferreira; Bastos, Víctor Alexandre Félix; Cossolin, Jamile Fernanda Silva; Serrão, José Éduardo; Bonetti, Ana Maria; Júnior, Luiz Carlos Oliveira; Ueira-Vieira, Carlos

doi:10.1016/j.neures.2022.02.003

Cited by 3 publications

(5 citation statements)

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“…This was identified as a significant therapeutic agent for treating mild cognitive impairment or conditions arising from cholinergic dysfunction 48 . In our study, we demonstrated that the methanolic extract of pollen from T. angustula , a stingless bee species, enhanced climbing ability and ameliorated damaged tissue in the D. melanogaster AD-like model, a primary behavioral assessment for screening novel anti-Alzheimer compounds in flies 49 .…”

Section: Discussionmentioning

confidence: 71%

Antioxidant and anti-Alzheimer's potential of Tetragonisca angustula (Jataí) stingless bee pollen

dos Santos,

Malta,

Franco

et al. 2024

Sci Rep

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Alzheimer's disease (AD) is considered the leading cause of dementia in the elderly worldwide. It results in progressive memory loss and impairment of cognitive and motor skills, leading to a high degree of disability and dependence. The development of AD is associated with the accumulation of senile plaques in the brain, caused by the amyloidogenic pathway of the disease. Several genetic and biochemical events are linked to AD development, with oxidative stress being one of them. Due to the scarcity of drugs aimed at treating AD, antioxidant compounds are increasingly studied as therapeutic targets for the disease. In this study, we investigate the antioxidant and anti-Alzheimer potential of the Tetragonisca angustula (Jataí) pollen extract in a Drosophila melanogaster Alzheimer's model. For this purpose, we utilized a D. melanogaster AD-like model, which expresses genes related to the amyloidogenic pathway of Alzheimer's disease. We explored the floral origin of the collected pollen, conducted phytochemical prospecting, and evaluated its antioxidant capacity in vitro. In vivo experiments involved assessing the survival and climbing ability of the D. melanogaster AD-like model with various concentrations of the pollen extract. Our findings revealed that the pollen extract of Tetragonisca angustula exhibits a significant antioxidant response and high concentrations of important phytochemicals, such as flavonoids and polyphenols. Furthermore, it enhanced the survival rate of D. melanogaster, and across all concentrations tested, it improved the climbing ability of the flies after 15 days of treatment with methanolic pollen extract. Additionally, the pollen extract reduced the neurodegeneration index in histopathological analysis. Thus, our study demonstrates the potential of Tetragonisca angustula pollen as an important subject for further investigation, aiming to isolate molecules that could potentially serve as therapeutic targets for Alzheimer's disease.

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Section: Discussionmentioning

confidence: 71%

Antioxidant and anti-Alzheimer's potential of Tetragonisca angustula (Jataí) stingless bee pollen

dos Santos,

Malta,

Franco

et al. 2024

Sci Rep

Self Cite

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“…The total number of DEGs found in 22 original works [ 30 , 32 , 35 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ] was 37,834 in 17 tissues of five animal species. Figure 2 shows our procedure of comparison of 37,834 animal ARD-linked DEGs ( Table 4 ) with the 39 PAG-related DEGs of the tame and aggressive rats ( Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…We have analyzed all publicly available independent experimental RNA-Seq datasets of the transcriptomes of tissues from ARD-susceptible versus ARD-resistant subjects (humans [ 33 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ] and animals [ 30 , 32 , 35 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ]) and the transcriptomes of tissues from domestic versus wild animals [ 68 , 74 , 204 , 205 , 206 , 207 , 208 , 209 , 210 , 211 ].…”

Section: Methodsmentioning

confidence: 99%

“…This could be why mainstream transcriptome-profiling studies of ARD susceptibility versus ARD resistance in human volunteers [ 33 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ] and animals [ 30 , 32 , 35 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ] are focused on the differentially expressed genes (DEGs) that are specific to gender, age, tissues, and pathogeneses. All previous research contributes to progress in predictive, preventive, personalized, participatory (4P) medicine [ 65 ] and helps us understand where, how, why, when, and what disorders can affect people depending on their genetic background, medical history, and lifestyle.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, we have recently profiled transcriptomes in the hippocampus [ 74 ] of tame versus aggressive rat strains, in which deficient β-protocadherins and β-hemoglobin were found to be the statistically significantly most common theranostic molecular markers for ARD-related hypertension. That is why we sequenced, in the same way, one more transcriptome, that of the periaqueductal gray matter (PAG), in the tame versus aggressive rats, identified the corresponding behavior-related PAG-associated DEGs in them, and compared these DEGs with their homologous PubMed-based [ 75 ] ARD-linked DEGs in animals [ 30 , 32 , 35 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 68 , 74 ] and humans [ 33 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ] to find out whether there are invariant molecular markers for such diseases among them.…”

Section: Introductionmentioning

confidence: 99%

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Differentially Expressed Genes and Molecular Susceptibility to Human Age-Related Diseases

Shikhevich

Chadaeva

Khandaev

et al. 2023

IJMS

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Mainstream transcriptome profiling of susceptibility versus resistance to age-related diseases (ARDs) is focused on differentially expressed genes (DEGs) specific to gender, age, and pathogeneses. This approach fits in well with predictive, preventive, personalized, participatory medicine and helps understand how, why, when, and what ARDs one can develop depending on their genetic background. Within this mainstream paradigm, we wanted to find out whether the known ARD-linked DEGs available in PubMed can reveal a molecular marker that will serve the purpose in anyone’s any tissue at any time. We sequenced the periaqueductal gray (PAG) transcriptome of tame versus aggressive rats, identified rat-behavior-related DEGs, and compared them with their known homologous animal ARD-linked DEGs. This analysis yielded statistically significant correlations between behavior-related and ARD-susceptibility-related fold changes (log2 values) in the expression of these DEG homologs. We found principal components, PC1 and PC2, corresponding to the half-sum and the half-difference of these log2 values, respectively. With the DEGs linked to ARD susceptibility and ARD resistance in humans used as controls, we verified these principal components. This yielded only one statistically significant common molecular marker for ARDs: an excess of Fcγ receptor IIb suppressing immune cell hyperactivation.

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Identification of bioactive peptides from a Brazilian kefir sample, and their anti-Alzheimer potential in Drosophila melanogaster

Malta

Batista

Silva

et al. 2022

Sci Rep

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Alzheimer’s disease (AD) is the most common form of dementia in the elderly, affecting cognitive, intellectual, and motor functions. Different hypotheses explain AD’s mechanism, such as the amyloidogenic hypothesis. Moreover, this disease is multifactorial, and several studies have shown that gut dysbiosis and oxidative stress influence its pathogenesis. Knowing that kefir is a probiotic used in therapies to restore dysbiosis and that the bioactive peptides present in it have antioxidant properties, we explored its biotechnological potential as a source of molecules capable of modulating the amyloidogenic pathway and reducing oxidative stress, contributing to the treatment of AD. For that, we used Drosophila melanogaster model for AD (AD-like flies). Identification of bioactive peptides in the kefir sample was made by proteomic and peptidomic analyses, followed by in vitro evaluation of antioxidant and acetylcholinesterase inhibition potential. Flies were treated and their motor performance, brain morphology, and oxidative stress evaluated. Finally, we performed molecular docking between the peptides found and the main pathology-related proteins in the flies. The results showed that the fraction with the higher peptide concentration was positive for the parameters evaluated. In conclusion, these results revealed these kefir peptide-rich fractions have therapeutic potential for AD.

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Differential gene expression by RNA-seq during Alzheimer’s disease-like progression in the Drosophila melanogaster model

Cited by 3 publications

References 58 publications

Antioxidant and anti-Alzheimer's potential of Tetragonisca angustula (Jataí) stingless bee pollen

Antioxidant and anti-Alzheimer's potential of Tetragonisca angustula (Jataí) stingless bee pollen

Differentially Expressed Genes and Molecular Susceptibility to Human Age-Related Diseases

Identification of bioactive peptides from a Brazilian kefir sample, and their anti-Alzheimer potential in Drosophila melanogaster

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