Academic Journal
An increase in ER stress and unfolded protein response in iPSCs-derived neuronal cells from neuronopathic Gaucher disease patients
| Title: | An increase in ER stress and unfolded protein response in iPSCs-derived neuronal cells from neuronopathic Gaucher disease patients |
|---|---|
| Authors: | Tanapat Pornsukjantra, Nongluk Saikachain, Nareerat Sutjarit, Arthaporn Khongkrapan, Alisa Tubsuwan, Kanit Bhukhai, Thipwimol Tim-Aroon, Usanarat Anurathapan, Suradej Hongeng, Nithi Asavapanumas |
| Source: | Scientific Reports, Vol 14, Iss 1, Pp 1-15 (2024) |
| Publisher Information: | Nature Portfolio, 2024. |
| Publication Year: | 2024 |
| Collection: | LCC:Medicine LCC:Science |
| Subject Terms: | Gaucher disease, iPSCs-derived neurons, ER stress, UPR, LSDs, Medicine, Science |
| More Details: | Abstract Gaucher disease (GD) is a lysosomal storage disorder caused by a mutation in the GBA1 gene, responsible for encoding the enzyme Glucocerebrosidase (GCase). Although neuronal death and neuroinflammation have been observed in the brains of individuals with neuronopathic Gaucher disease (nGD), the exact mechanism underlying neurodegeneration in nGD remains unclear. In this study, we used two induced pluripotent stem cells (iPSCs)-derived neuronal cell lines acquired from two type-3 GD patients (GD3-1 and GD3-2) to investigate the mechanisms underlying nGD by biochemical analyses. These iPSCs-derived neuronal cells from GD3-1 and GD3-2 exhibit an impairment in endoplasmic reticulum (ER) calcium homeostasis and an increase in unfolded protein response markers (BiP and CHOP), indicating the presence of ER stress in nGD. A significant increase in the BAX/BCL-2 ratio and an increase in Annexin V-positive cells demonstrate a notable increase in apoptotic cell death in GD iPSCs-derived neurons, suggesting downstream signaling after an increase in the unfolded protein response. Our study involves the establishment of iPSCs-derived neuronal models for GD and proposes a possible mechanism underlying nGD. This mechanism involves the activation of ER stress and the unfolded protein response, ultimately leading to apoptotic cell death in neurons. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-024-59834-6 |
| Access URL: | https://doaj.org/article/0f6e96ed824b4ccca62b25c09c125f40 |
| Accession Number: | edsdoj.0f6e96ed824b4ccca62b25c09c125f40 |
| Database: | Directory of Open Access Journals |
| Full text is not displayed to guests. | Login for full access. |
| ISSN: | 20452322 |
|---|---|
| DOI: | 10.1038/s41598-024-59834-6 |
| Published in: | Scientific Reports |
| Language: | English |