Efecto del ácido ascórbico en la Drosophila transgénica que expresa Aβ-42 humano en las neuronas

Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by the accumulation of amyloid-beta (Aβ) peptides, especially the toxic Aβ42 isoform, which induces excessive reactive oxygen species (ROS) production leading to oxidative damage, lipid peroxidation, and neuronal loss. Given the critical role of oxidative stress in AD pathogenesis, antioxidants such as ascorbic acid (AA) are being explored for their therapeutic potential.

This study aimed to investigate the neuroprotective efficacy of ascorbic acid in a transgenic Drosophila melanogaster model expressing human Aβ42 in neuronal tissues.

Transgenic and wild-type flies were maintained on diets supplemented with optimized, non-toxic concentrations of AA. Biochemical assays were performed to evaluate oxidative stress and antioxidant defense, including glutathione (GSH) levels, glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid-reactive substances (TBARS), and protein carbonyl content (PCC). Acetylcholinesterase (AChE) activity and locomotor performance were also assessed.

Ascorbic acid supplementation significantly enhanced GSH levels, normalized GST, SOD, and CAT activities, and reduced TBARS and PCC levels, indicating restoration of redox balance. Partial recovery of AChE activity suggested protection of cholinergic neurotransmission. Functionally, AA-fed AD flies exhibited improved locomotor performance, delayed onset of memory impairment, and extended lifespan compared to untreated AD flies.

The findings demonstrate that ascorbic acid provides multifaceted neuroprotection by mitigating oxidative stress, stabilizing cholinergic function, improving behavioural outcomes, and enhancing longevity. AA emerges as a promising, low-cost natural antioxidant for potential use in Alzheimer's disease management.