Cytogenetic Analysis of the Results of Genome Editing on the Cell Model of Parkinson’s Disease

Ветчинова, А. С.; Simonova, V. V.; Новосадова, Е. В.; Manuilova, Ekaterina; Nenasheva, Valentina V.; Tarantul, V. Z.; Гривенников, И. А.; Хаспеков, Л. Г.; Иллариошкин, С. Н.

doi:10.1007/s10517-018-4174-y

Cited by 10 publications

(4 citation statements)

References 13 publications

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“…The high expression level of a serine/threonine protein kinase, which is recruited and activated by double-strand DNA breaks, in neurons of patients with a mutation in the LRRK2 gene, may be due to the interaction of the mutant guanosine triphosphatedependent kinase with lamin B1 protein, associated with the inner nuclear membrane and involved in nuclear skeleton formation. This pathological interaction contributes to chromatin instability and disruption of the cell cycle [47]. ATM plays a crucial role in cell cycle arrest following DNA damage, particularly after double-strand breaks.…”

Section: Increased Gene Expressionmentioning

confidence: 99%

Mitochondrial Dysfunction in Dopaminergic Neurons Derived from Patients with LRRK2- and SNCA-Associated Genetic Forms of Parkinson’s Disease

Vetchinova,

Kapkaeva,

Ivanov

et al. 2023

CIMB

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Parkinson’s disease (PD) is the second most common neurodegenerative disease. Some cases of PD may be caused by genetic factors, among which mutations in the LRRK2 and SNCA genes play an important role. To develop effective neuroprotective strategies for PD, it is important to diagnose the disease at the earliest stages of the neurodegenerative process. Therefore, the detection of diagnostic and prognostic markers of Parkinson’s disease (PD) is an urgent medical need. Advances in induced pluripotent stem cell (iPSC) culture technology provide new opportunities for the search for new biomarkers of PD and its modeling in vitro. In our work, we used a new technology for multiplex profiling of gene expression using barcoding on the Nanostring platform to assess the activity of mitochondrial genes on iPSC-derived cultures of dopaminergic neurons obtained from patients with LRRK2- and SNCA-associated genetic forms PD and a healthy donor. Electron microscopy revealed ultrastructural changes in mitochondria in both LRRK2 and SNCA mutant cells, whereas mitochondria in cells from a healthy donor were normal. In a culture with the SNCA gene mutation, the ratio of the area occupied by mitochondria to the total area of the cytoplasm was significantly lower than in the control and in the line with the LRRK2 gene mutation. Transcriptome analysis of 105 mitochondria proteome genes using the Nanostring platform revealed differences between the diseased and normal cells in the activity of genes involved in respiratory complex function, the tricarboxylic acid cycle, ATP production, mitochondria–endoplasmic reticulum interaction, mitophagy, regulation of calcium concentration, and mitochondrial DNA replication.

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Section: Increased Gene Expressionmentioning

confidence: 99%

Mitochondrial Dysfunction in Dopaminergic Neurons Derived from Patients with LRRK2- and SNCA-Associated Genetic Forms of Parkinson’s Disease

Vetchinova,

Kapkaeva,

Ivanov

et al. 2023

CIMB

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“…Several researchers have proposed creating an LRRK2-related PD stem cell model [149]. Mutations in the LRRK2, associated with its enhanced aberrant activity and resulting in DNs toxicity, are the most common genetic cause of sporadic and familial PD.…”

Section: Disease Modeling and Genetic Screeningmentioning

confidence: 99%

CRISPR-Cas9-Based Technology and Its Relevance to Gene Editing in Parkinson’s Disease

et al. 2022

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Parkinson’s disease (PD) and other chronic and debilitating neurodegenerative diseases (NDs) impose a substantial medical, emotional, and financial burden on individuals and society. The origin of PD is unknown due to a complex combination of hereditary and environmental risk factors. However, over the last several decades, a significant amount of available data from clinical and experimental studies has implicated neuroinflammation, oxidative stress, dysregulated protein degradation, and mitochondrial dysfunction as the primary causes of PD neurodegeneration. The new gene-editing techniques hold great promise for research and therapy of NDs, such as PD, for which there are currently no effective disease-modifying treatments. As a result, gene therapy may offer new treatment options, transforming our ability to treat this disease. We present a detailed overview of novel gene-editing delivery vehicles, which is essential for their successful implementation in both cutting-edge research and prospective therapeutics. Moreover, we review the most recent advancements in CRISPR-based applications and gene therapies for a better understanding of treating PD. We explore the benefits and drawbacks of using them for a range of gene-editing applications in the brain, emphasizing some fascinating possibilities.

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“…In contrast, overexpression of P13 has been shown to promote the emergence of phenotypes in toxin-induced PD mice ( Inoue et al, 2018 ). Some researchers have proposed references for the construction of a LRRK2-related PD stem cell model through cytogenetic analysis ( Vetchinova et al, 2018 ). Another LRRK2 iPSC model constructed with the TALEN technique could additionally serve as a reference ( Ohta et al, 2020 ).…”

Section: Parkinson’s Diseasementioning

confidence: 99%

Gene Therapy for Neurodegenerative Disease: Clinical Potential and Directions

Zhu

Yang

Hao

et al. 2021

Front. Mol. Neurosci.

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The pathogenesis of neurodegenerative diseases (NDDs) is complex and diverse. Over the decades, our understanding of NDD has been limited to pathological features. However, recent advances in gene sequencing have facilitated elucidation of NDD at a deeper level. Gene editing techniques have uncovered new genetic links to phenotypes, promoted the development of novel treatment strategies and equipped researchers with further means to construct effective cell and animal models. The current review describes the history of evolution of gene editing tools, with the aim of improving overall understanding of this technology, and focuses on the four most common NDD disorders to demonstrate the potential future applications and research directions of gene editing.

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Cytogenetic Analysis of the Results of Genome Editing on the Cell Model of Parkinson’s Disease

Cited by 10 publications

References 13 publications

Mitochondrial Dysfunction in Dopaminergic Neurons Derived from Patients with LRRK2- and SNCA-Associated Genetic Forms of Parkinson’s Disease

Mitochondrial Dysfunction in Dopaminergic Neurons Derived from Patients with LRRK2- and SNCA-Associated Genetic Forms of Parkinson’s Disease

CRISPR-Cas9-Based Technology and Its Relevance to Gene Editing in Parkinson’s Disease

Gene Therapy for Neurodegenerative Disease: Clinical Potential and Directions

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