CRISPR/Cas9 novel therapeutic road for the treatment of neurodegenerative diseases

Karimian, Ansar; Gorjizadeh, Negar; Alemi, Forough; Asemi, Zatollah; Azizian, Khalil; Soleimanpour, Jafar; Malakouti, Faezeh; Targhazeh, Niloufar; Majidinia, Maryam; Yousefi, Bahman

doi:10.1016/j.lfs.2020.118165

Cited by 35 publications

(31 citation statements)

References 55 publications

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“…Gene editing is accurate and involves targeted cleavage of specific double stranded sequence of the DNA and utilization of various DNA repair pathways. Cleavage is mainly performed by nucleases namely, ZFN, TALEN, meganucleases, and CRISPR-Cas-9 system [374]. CRISPR is gaining a lot of attention these days due to lacunae in effective treatment of neurological disorders.…”

Section: Crispr-cas Systemmentioning

confidence: 99%

Gene Therapy Approach with an Emphasis on Growth Factors: Theoretical and Clinical Outcomes in Neurodegenerative Diseases

et al. 2021

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The etiology of many neurological diseases affecting the central nervous system (CNS) is unknown and still needs more effective and specific therapeutic approaches. Gene therapy has a promising future in treating neurodegenerative disorders by correcting the genetic defects or by therapeutic protein delivery and is now an attraction for neurologists to treat brain disorders, like Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, spinocerebellar ataxia, epilepsy, Huntington's disease, stroke, and spinal cord injury. Gene therapy allows the transgene induction, with a unique expression in cells' substrate. This article mainly focuses on the delivering modes of genetic materials in the CNS, which includes viral and non-viral vectors and their application in gene therapy. Despite the many clinical trials conducted so far, data have shown disappointing outcomes. The efforts done to improve outcomes, efficacy, and safety in the identification of targets in various neurological disorders are also discussed here. Adapting gene therapy as a new therapeutic approach for treating neurological disorders seems to be promising, with early detection and delivery of therapy before the neuron is lost, helping a lot the development of new therapeutic options to translate to the clinic.

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Section: Crispr-cas Systemmentioning

confidence: 99%

Gene Therapy Approach with an Emphasis on Growth Factors: Theoretical and Clinical Outcomes in Neurodegenerative Diseases

et al. 2021

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“…These gene knock-out models have been employed extensively toward refining searches for genetic disease susceptibility loci. In preclinical models of AD, most CRISPR-Cas9 mediated therapies are directed toward inhibiting the neurotoxic form of Aβ proteins and deactivation of γ -secretase activating protein (Karimian et al, 2020), and have demonstrated encouraging results toward their therapeutic application in both FAD and LOAD. The CRISPR-Cas9 system has also been utilized to generate numerous knockout models of inflammatory arthritis and OP.…”

Section: Alternative Treatment Paradigmsmentioning

confidence: 99%

The Role of Chronic Inflammatory Bone and Joint Disorders in the Pathogenesis and Progression of Alzheimer's Disease

Culibrk

Hahn

2020

Front. Aging Neurosci.

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Late-onset Alzheimer's Disease (LOAD) is a devastating neurodegenerative disorder that causes significant cognitive debilitation in tens of millions of patients worldwide. Throughout disease progression, abnormal secretase activity results in the aberrant cleavage and subsequent aggregation of neurotoxic Aβ plaques in the cerebral extracellular space and hyperphosphorylation and destabilization of structural tau proteins surrounding neuronal microtubules. Both pathologies ultimately incite the propagation of a disease-associated subset of microglia—the principle immune cells of the brain—characterized by preferentially pro-inflammatory cytokine secretion and inhibited AD substrate uptake capacity, which further contribute to neuronal degeneration. For decades, chronic neuroinflammation has been identified as one of the cardinal pathophysiological driving features of AD; however, despite a number of works postulating the underlying mechanisms of inflammation-mediated neurodegeneration, its pathogenesis and relation to the inception of cognitive impairment remain obscure. Moreover, the limited clinical success of treatments targeting specific pathological features in the central nervous system (CNS) illustrates the need to investigate alternative, more holistic approaches for ameliorating AD outcomes. Accumulating evidence suggests significant interplay between peripheral immune activity and blood-brain barrier permeability, microglial activation and proliferation, and AD-related cognitive decline. In this work, we review a narrow but significant subset of chronic peripheral inflammatory conditions, describe how these pathologies are associated with the preponderance of neuroinflammation, and posit that we may exploit peripheral immune processes to design interventional, preventative therapies for LOAD. We then provide a comprehensive overview of notable treatment paradigms that have demonstrated considerable merit toward treating these disorders.

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“…This system is very useful to create disease models or to discover new etiological agents, allowing researchers to better understand their biology. Examples include cancer, neurological diseases, cardiovascular diseases, immunodeficiency, infectious diseases, sickle cell disease, hemophilia, metabolic diseases, cystic fibrosis, retinitis pigmentosa, and several others (reviewed in [ 36 , 37 , 38 , 39 , 40 , 41 , 42 ]). In particular, the treatment and characterization of cancer is very promising, and hundreds of publications are available on this topic (for recent reviews, see for example [ 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ]).…”

Section: Introductionmentioning

confidence: 99%

CRISPR-Cas and Its Wide-Ranging Applications: From Human Genome Editing to Environmental Implications, Technical Limitations, Hazards and Bioethical Issues

Piergentili

Rio

Signore

et al. 2021

Cells

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The CRISPR-Cas system is a powerful tool for in vivo editing the genome of most organisms, including man. During the years this technique has been applied in several fields, such as agriculture for crop upgrade and breeding including the creation of allergy-free foods, for eradicating pests, for the improvement of animal breeds, in the industry of bio-fuels and it can even be used as a basis for a cell-based recording apparatus. Possible applications in human health include the making of new medicines through the creation of genetically modified organisms, the treatment of viral infections, the control of pathogens, applications in clinical diagnostics and the cure of human genetic diseases, either caused by somatic (e.g., cancer) or inherited (mendelian disorders) mutations. One of the most divisive, possible uses of this system is the modification of human embryos, for the purpose of preventing or curing a human being before birth. However, the technology in this field is evolving faster than regulations and several concerns are raised by its enormous yet controversial potential. In this scenario, appropriate laws need to be issued and ethical guidelines must be developed, in order to properly assess advantages as well as risks of this approach. In this review, we summarize the potential of these genome editing techniques and their applications in human embryo treatment. We will analyze CRISPR-Cas limitations and the possible genome damage caused in the treated embryo. Finally, we will discuss how all this impacts the law, ethics and common sense.

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CRISPR/Cas9 novel therapeutic road for the treatment of neurodegenerative diseases

Cited by 35 publications

References 55 publications

Gene Therapy Approach with an Emphasis on Growth Factors: Theoretical and Clinical Outcomes in Neurodegenerative Diseases

Gene Therapy Approach with an Emphasis on Growth Factors: Theoretical and Clinical Outcomes in Neurodegenerative Diseases

The Role of Chronic Inflammatory Bone and Joint Disorders in the Pathogenesis and Progression of Alzheimer's Disease

CRISPR-Cas and Its Wide-Ranging Applications: From Human Genome Editing to Environmental Implications, Technical Limitations, Hazards and Bioethical Issues

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