ArticleInternational journal of molecular sciences2017
CRISPR-Cas9 Mediated Telomere Removal Leads to Mitochondrial Stress and Protein Aggregation.
Article in International journal of molecular sciences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 30 citations in OpenAlex.
- Ultrasound Control of Genomic Regulatory Toolboxes for Cancer Immunotherapy.Nature communications · 2024Article
- Engineered FSHD mutations results in D4Z4 heterochromatin disruption and feedforward DUX4 network activation.iScience · 2024Article
- Retinal Organoids: A Next-Generation Platform for High-Throughput Drug Discovery.Stem cell reviews and reports · 2024Review
- Combining old and new concepts in targeting telomerase for cancer therapy: transient, immediate, complete and combinatory attack (TICCA).Cancer cell international · 2023Review
- CRISPR/Cas9 assisted stem cell therapy in Parkinson's disease.Biomaterials research · 2023Review
- CRISPR/Cas: A New Tool in the Research of Telomeres and Telomerase as Well as a Novel Form of Cancer Therapy.International journal of molecular sciences · 2022Review
- Retinal Organoids and Retinal Prostheses: An Overview.International journal of molecular sciences · 2022Review
- LPM3770277, a Potent Novel CDK4/6 Degrader, Exerts Antitumor Effect Against Triple-Negative Breast Cancer.Frontiers in pharmacology · 2022Article
- Accelerated telomere shortening independent of LRRK2 variants in Chinese patients with Parkinson's disease.Aging · 2020Article
- Degradation of proteins by PROTACs and other strategies.Acta pharmaceutica Sinica. B · 2020Review
- Strategies for the Treatment of Parkinson's Disease: Beyond Dopamine.Frontiers in aging neuroscience · 2020Article
- Accelerated aging in serious mental disorders.Current opinion in psychiatry · 2019Review
- Targeting Telomeres and Telomerase: Studies in Aging and Disease Utilizing CRISPR/Cas9 Technology.Cells · 2019Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aging is considered the major risk factor for neurodegenerative diseases including Parkinson's disease (PD). Telomere shortening is associated with cellular senescence. In this regard, pharmacological or genetic inhibition of telomerase activity has been used to model cellular aging. Here, we employed CRISPR-Cas9 technology to instantly remove the telomere to induce aging in a neuroblastoma cell line. Expression of both Cas9 and guide RNA targeting telomere repeats ablated the telomere, leading to retardation of cell proliferation. Instant deletion of telomere in SH-SY5Y cells impaired mitochondrial function with diminished mitochondrial respiration and cell viability. Supporting the pathological relevance of cell aging by CRISPR-Cas9 mediated telomere removal, alterations were observed in the levels of PD-associated proteins including PTEN-induced putative kinase 1, peroxisome proliferator-activated receptor γ coactivator 1-α, nuclear respiratory factor 1, parkin, and aminoacyl tRNA synthetase complex interacting multifunctional protein 2. Significantly, α-synuclein expression in the background of telomere removal led to the enhancement of protein aggregation, suggesting positive feed-forward interaction between aging and PD pathogenesis. Collectively, our results demonstrate that CRISPR-Cas9 can be used to efficiently model cellular aging and PD.
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