Cellular and Molecular Neurobiology
Author: Micaela Daiana Garcia | Email: mdgarcia@fmed.uba.ar
Micaela Daiana Garcia1°, Belén Favarolo1°,Cayetana Arnaiz2°, Julieta Bianchelli2°, Pedro Miarnau2°, Tomás Falzone1°2°, Mariana Holubiec1°2°
1° Instituto de Biología Celular y Neurociencia, Facultad de Medicina, (IBCN-UBA-CONICET), Argentina.
2° Instituto de Investigación en Biomedicina de Buenos Aires – Instituto Partner de la Sociedad Max Planck (IBioBA-MPSP-CONICET), Argentina.
Many functions have been attributed to the amyloid precursor protein (APP), that through γ and β secretase processing might modulate mitochondrial homeostasis. Increased β amyloid peptides (Aβ) levels,a byproduct of this processing, are considered one of the main hallmarks of Alzheimer’s disease (AD). However, it has been shown that redox regulation and mitochondrial homeostasis precede the appearance of Aβ aggregates, indicating the presence of a molecular mechanism that is independent of Aβ. Bisphenol-A (BPA), a compound present in a variety of local consumption elements, has been linked to neurodegeneration and AD. However, BPA is a γ secretase inhibitor, which would decrease Aβ levels. Interestingly, this enzyme is also involved in the Wnt/β-Catenin (Wnt/β-Cat) pathway. Here, we aim to determine if the neurodegenerative action of BPA is linked to mitochondrial redox regulation through the Wnt/β-Cat pathway, mediated by APP. Preliminary results show that BPA treatment decreases nuclear localization of β-Cat in cultured human neurons. Furthermore, BPA increases both mitochondrial length and membrane polarization in the axons of glutamatergic human neurons. These results indicate that BPA might affect the Wnt/β-Cat pathway and mitochondrial homeostasis. Future experiments are aimed to determine if BPA exacerbates metabolic and mitochondrial alterations through the Wnt/β-Cat pathway acting on mitochondrial membrane APP in human models of AD.