Validação do potencial antineurodegenerativo do peptídeo P5LFM-BSB, em Drosophila melanogaster modelo de doença de Alzheimer

Abstract

Alzheimer’s disease is the leading cause of dementia worldwide and represents one of the greatest public health challenges of the 21st century. It is characterized by the accumulation of β-amyloid peptide (Aβ) in brain tissue. Given the limitations of currently available treatments and the challenges associated with developing effective inhibitors of the enzyme BACE1, responsible for the rate-limiting step of the amyloidogenic pathway, the search for new bioactive molecules with neuroprotective potential becomes imperative. In this context, the present study investigated the antineurodegenerative potential of the synthetic peptide P5LFMBSB (Peptide 5 from the larval food microbiome of Brazilian stingless bees), derived from the secretome of bacteria isolated from the larval food of Brazilian stingless bees, using a transgenic Drosophila melanogaster line as a model of Alzheimer’s disease. To this end, peptide toxicity was assessed through eclosion and metamorphosis progression assays, as well as its effects on the neurodegenerative phenotype through qualitative and quantitative analyses of the fly eye surface, using scanning electron microscopy and the Flynotyper plugin. The experimental model was previously validated, showing significant disorganization of ommatidia in the ADlike genotype compared to the control line UAS-Aβ/+. The peptide P5LFM-BSB did not exhibit toxicity at the tested concentrations (25, 50, 100, and 200 µM), and treated groups showed a reduction in the degree of ommatidial disorganization compared to the untreated group, with a statistically significant difference at the 50 µM concentration. These results indicate that the peptide P5LFM-BSB exhibits antineurodegenerative activity when evaluated in a Drosophila melanogaster rough eye model, highlighting its potential as a promising molecule for the development of new therapeutic strategies for Alzheimer’s disease.