Monitoring the interactions between alpha-synuclein and Tau in vitro and in vivo using bimolecular fluorescence complementation

• Published in: Scientific reports Vol. 12; no. 1; p. 2987
• Main Authors: Torres-Garcia, Laura, P. Domingues, Joana M., Brandi, Edoardo, Haikal, Caroline, Mudannayake, Janitha M., Brás, Inês C., Gerhardt, Ellen, Li, Wen, Svanbergsson, Alexander, Outeiro, Tiago F., Gouras, Gunnar K., Li, Jia-Yi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22-02-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378; 631/378/1689/1283; 631/378/1689/1718; 631/378/1689/364; alpha-Synuclein - metabolism; Alzheimer's disease; Amyloidogenesis; Animal models; Animals; Basic Medicine; Cell Line, Tumor; Cell lines; Fluorescence; Fluorescent Antibody Technique - methods; HEK293 Cells; Humanities and Social Sciences; Humans; In Vitro Techniques; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Mice; Movement disorders; multidisciplinary; Neuroblastoma; Neuroblasts; Neurodegenerative diseases; Neurosciences; Neurovetenskaper; Parkinson's disease; Protein Aggregates; Protein interaction; Protein Interaction Maps; Proteins; Rats; Science; Science (multidisciplinary); Substantia nigra; Synuclein; Tau protein; tau Proteins - metabolism; β-Amyloid
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-06846-9

Parkinson’s disease (PD) and Alzheimer’s disease (AD) are characterized by pathological accumulation and aggregation of different amyloidogenic proteins, α-synuclein (aSyn) in PD, and amyloid-β (Aβ) and Tau in AD. Strikingly, few PD and AD patients’ brains exhibit pure pathology with most cases presenting mixed types of protein deposits in the brain. Bimolecular fluorescence complementation (BiFC) is a technique based on the complementation of two halves of a fluorescent protein, which allows direct visualization of protein–protein interactions. In the present study, we assessed the ability of aSyn and Tau to interact with each other. For in vitro evaluation, HEK293 and human neuroblastoma cells were used, while in vivo studies were performed by AAV6 injection in the substantia nigra
pars compacta
(SNpc) of mice and rats. We observed that the co-expression of aSyn and Tau led to the emergence of fluorescence, reflecting the interaction of the proteins in cell lines, as well as in mouse and rat SNpc. Thus, our data indicates that aSyn and Tau are able to interact with each other in a biologically relevant context, and that the BiFC assay is an effective tool for studying aSyn-Tau interactions in vitro and in different rodent models in vivo.