Reference - Detail
| RRC ID | 73807 |
|---|---|
| Author | Inoue S, Nishimura K, Gima S, Nakano M, Takata K. |
| Title | CRISPR-Cas9-Edited SNCA Knockout Human Induced Pluripotent Stem Cell-Derived Dopaminergic Neurons and Their Vulnerability to Neurotoxicity. |
| Journal | Biol Pharm Bull |
| Abstract |
Parkinson's disease (PD) is an age-related disorder with selective dopaminergic (DA) neuronal degeneration in the substantia nigra pars compacta. The presence of mainly α-synuclein-composed Lewy bodies in DA neurons is among the disease hallmarks in the brain of patients with PD. Human induced pluripotent stem cells (hiPSCs) are powerful tools to investigate PD pathophysiology and understand its molecular and cellular mechanisms better. In this study, we generated an α-synuclein-null hiPSC line introducing a nonsense mutation in the α-synuclein-encoding SNCA alleles using clustered regularly interspaced short palindromic repeats CRISPR-associated protein 9 (CRISPR-Cas9)-mediated gene editing. Our Western blotting analysis revealed the lack of α-synuclein protein expression in SNCA knockout hiPSC-derived cells. In addition, SNCA knockout hiPSCs retained healthy cell morphology, undifferentiated marker gene (e.g., NANOG, POU5F1, and SOX2) expression, and differentiation ability (based on the marker gene expression levels of the three germ layers). Finally, SNCA knockout hiPSC-derived DA neurons exhibited reduced vulnerability to the DA neurotoxin, 1-methyl-4-phenylpyridinium. In conclusion, the SNCA knockout hiPSC line we generated would provide a useful experimental tool for studying the physiological and pathological role of α-synuclein in PD. |
| Volume | 46(3) |
| Pages | 517-522 |
| Published | 2023-1-1 |
| DOI | 10.1248/bpb.b22-00839 |
| PMID | 36858582 |
| MeSH | CRISPR-Cas Systems Dopamine Dopaminergic Neurons Gene Expression Humans Induced Pluripotent Stem Cells* Neurotoxicity Syndromes* Parkinson Disease* alpha-Synuclein |
| IF | 1.863 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 10 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | 1231A3(HPS0381) |