Informace o publikaci
Unraveling the link between alzheimer’s disease and herpes simplex virus using induced pluripotent stem cells-derived brain organoids
| Autoři | |
|---|---|
| Rok publikování | 2023 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Alzheimer’s disease (AD) is a progressive neurological disorder characterized by memory loss, cognitive decline, and behavioral changes. While the exact cause of AD remains unknown, recent studies have proposed a potential role of herpes simplex virus type 1 (HSV-1) in its development. The connection between AD and HSV-1 may involve Amyloid beta (Aß), a peptide composed of 39-42 amino acids derived from the APP protein, which forms plaques in the brains of Alzheimer’s patients. Aß seems to function as an antimicrobial peptide, potentially aiding in the defense against HSV-1 infection. In our project, we utilized both 2D neurons and 3D brain organoids derived from healthy individuals and those with familial Alzheimer’s disease (fAD) to investigate the impact of viral infection on AD pathology. Remarkably, HSV-1 infection, along with extracellular Aß40 and Aß42 treatment, resulted in the accumulation of APP protein and the growth of APP clusters, confirming their role as antimicrobial peptides. Intriguingly, fAD organoids responded to infection by reducing the amount of APP while increasing the Aß42/40 ratio in the medium. Additionally, mRNA sequencing of fAD organoids after HSV-1 infection revealed decreased metabolism-related processes. Though further research is necessary to fully comprehend the relationship between viral infection and Alzheimer’s disease, our findings suggest that Aß peptides likely contribute to the formation of APP clusters in brain organoids derived from human pluripotent stem cells. |