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image of Effect of Ascorbic Acid on the Transgenic Drosophila Expressing Human Aβ-42 in the Neurons

Abstract

Background

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by extracellular accumulation of amyloid-beta (Aβ) peptides, particularly the toxic Aβ42 isoform. Aβ42 aggregation induces excessive reactive oxygen species (ROS) production, resulting in oxidative damage, lipid peroxidation, protein oxidation, and neuronal dysfunction. Oxidative stress plays a pivotal role in AD pathogenesis, making antioxidants promising therapeutic candidates.

Objective

The present study aimed to evaluate the neuroprotective efficacy of ascorbic acid (AA), a potent dietary antioxidant, in a transgenic model of AD expressing human Aβ42 in neuronal tissues.

Materials and Methods

Transgenic expressing human Aβ42 under a neuronal driver were used as the AD model, with wild-type flies as controls. Flies were supplemented with optimized, non-toxic doses of AA throughout their lifespan. Oxidative stress and antioxidant defense were assessed using glutathione (GSH) levels, glutathione S-transferase (GST), thiobarbituric acid-reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), protein carbonyl content (PCC), and acetylcholinesterase (AChE) activity. Locomotor performance was evaluated using the negative geotaxis assay.

Results

AA supplementation significantly restored redox homeostasis by increasing GSH levels and reducing TBARS and PCC. Antioxidant enzyme activities (GST, SOD, and CAT) were normalized, accompanied by partial restoration of AChE activity. AA-fed AD flies exhibited improved locomotor performance, delayed cognitive decline, and extended lifespan compared to untreated AD flies.

Discussion

The findings indicate that AA mitigates Aβ42-induced oxidative stress by enhancing endogenous antioxidant defenses and reducing oxidative damage. The improvement in AChE activity suggests preservation of cholinergic neurotransmission, which is crucial for learning and memory. Behavioral recovery and lifespan extension further demonstrate the systemic neuroprotective effects of AA, supporting its role as a multifunctional modulator of AD-associated pathology.

Conclusion

This study highlights the multidimensional neuroprotective potential of ascorbic acid in a transgenic AD model. By alleviating oxidative stress, preserving cholinergic function, improving behavior, and promoting longevity, AA emerges as a promising, low-cost antioxidant for further evaluation in higher animal models and clinical settings.

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2026-01-05
2026-02-27

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Effect of Ascorbic Acid on the Transgenic Drosophila Expressing Human Aβ-42 in the Neurons
Bentham Science Publishers ; https://doi.org/10.2174/0115672050403064251130163451
/content/journals/car/10.2174/0115672050403064251130163451
/content/journals/car/10.2174/0115672050403064251130163451
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  • Article Type:     Research Article
Keywords: Ascorbic acid ; cognitive ; neurons ; Drosophila ; human Aβ42 ; oxidative stress

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