Causative Genes in Amyotrophic Lateral Sclerosis and Protein Degradation Pathways: a Link to Neurodegeneration

Maurel, Cindy; Dangoumau, Audrey; Marouillat, Sylviane; Brulard, Céline; Chami, Anna A.; Hergesheimer, Rudolf; Corcia, Philippe; Blasco, Hélène; Andres, Christian R.; Vourc’h, Patrick

doi:10.1007/s12035-017-0856-0

Cited by 55 publications

(39 citation statements)

References 227 publications

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“…Amyotrophic lateral sclerosis (AML) is a neurodegenerative disease characterized by motor deficits, which can also be associated with cognitive and behavioural changes. In most cases the mechanisms causing the disease are unknown, called sporadic ALS, but in a subset of patients the disease is familial involving mutations in the genes C9orf72, TARDBP (TDP43), FUS and superoxide dismutase (SOD1) among others [176][177][178][179][180]. One hypothesis is that the degeneration of motor neurons in AML caused by mutated versions of SOD1, might be associated with the tendency of mutant SOD1 versions to misfold and aggregate [176].…”

Section: Further Applications In Neurobiologymentioning

confidence: 99%

Applying Antibodies Inside Cells: Principles and Recent Advances in Neurobiology, Virology and Oncology

et al. 2020

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To interfere with cell function, many scientists rely on methods that target DNA or RNA due to the ease with which they can be applied. Proteins are usually the final executors of function but are targeted only indirectly by these methods. Recent advances in targeted degradation of proteins based on proteolysis-targeting chimaeras (PROTACs), ubiquibodies, deGradFP (degrade Green Fluorescent Protein) and other approaches have demonstrated the potential of interfering directly at the protein level for research and therapy. Proteins can be targeted directly and very specifically by antibodies, but using antibodies inside cells has so far been considered to be challenging. However, it is possible to deliver antibodies or other proteins into the cytosol using standard laboratory equipment. Physical methods such as electroporation have been demonstrated to be efficient and validated thoroughly over time. The expression of intracellular antibodies (intrabodies) inside cells is another way to interfere with intracellular targets at the protein level. Methodological strategies to target the inside of cells with antibodies, including delivered antibodies and expressed antibodies, as well as applications in the research areas of neurobiology, viral infections and oncology, are reviewed here. Antibodies have already been used to interfere with a wide range of intracellular targets. Disease-related targets included proteins associated with neurodegenerative diseases such as Parkinson's disease (α-synuclein), Alzheimer's disease (amyloid-β) or Huntington's disease (mutant huntingtin [mHtt]). The applications of intrabodies in the context of viral infections include targeting proteins associated with HIV (e.g. HIV1-TAT, Rev, Vif, gp41, gp120, gp160) and different oncoviruses such as human papillomavirus (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV) and Epstein-Barr virus, and they have been used to interfere with various targets related to different processes in cancer, including oncogenic pathways, proliferation, cell cycle, apoptosis, metastasis, angiogenesis or neo-antigens (e.g. p53, human epidermal growth factor receptor-2 [HER2], signal transducer and activator of transcription 3 [STAT3], RAS-related RHO-GTPase B (RHOB), cortactin, vascular endothelial growth factor receptor 2 [VEGFR2], Ras, Bcr-Abl). Interfering at the protein level allows questions to be addressed that may remain unanswered using alternative methods. This review addresses why direct targeting of proteins allows unique insights, what is currently feasible in vitro, and how this relates to potential therapeutic applications.Therapeutic antibodies are valuable drugs, which mostly act outside of cells.Reaching the numerous drug targets that reside inside cells by antibodies is possible in vitro and allows unique insights compared with other methods.Applying antibodies inside cells for therapeutic purposes has been explored in animal models and promises specific therapeutic benefits in neurobiology, virology and oncology.

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Section: Further Applications In Neurobiologymentioning

confidence: 99%

Applying Antibodies Inside Cells: Principles and Recent Advances in Neurobiology, Virology and Oncology

et al. 2020

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“…The TARDBP gene mutation was found in 5% of FALS cases and 1% in SALS cases. Till now, more than 50 different mutations have been identified [9]. Except for D169G, a majority of these mutations are located in the 3′ region encoding a glycine-rich domain in its product, TDP-43.…”

Section: Tardbpmentioning

confidence: 99%

Novel Aspects on Motor Neuron Disease: The Recent Genetic Studies on ALS

Wang¹

2020

Novel Aspects on Motor Neuron Disease

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At present, with the advanced affordable genetic testing, the rate of discovering amyotrophic lateral sclerosis (ALS)-related genes rapidly increases. These genetic findings provide new insights into therapies that target genetic subset of ALS. However, the research on the genetic and environmental causes of ALS is still in the early stage. In this chapter, we review the current understanding of ALS-related genes and summarize the worldwide ALS distribution feature by the frequency of occurrence in different regions. We summarize the advances in genetic testing and counseling for ALS. Based on the increase in genetic testing, we believe that the ALS patients and families would be benefited from our studies in the near future.

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“…Современные методы генетических исследований позволяют выявить мутантные гены в 68 % семейных и 11 % спорадических случаев БАС. Наиболее часто определяют мутации в генах SOD-1, FUS, TDP-43 и C9orf72 [19].…”

Section: патогенез бокового амиотрофического склерозаunclassified

Amyotrophic lateral sclerosis: pathogenetic mechanisms and new approaches to pharmacotherapy (literature review)

Алексеева

Стучевская

Демешонок

2019

Neuromuscular Diseases

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Amyotrophic lateral sclerosis is a neurodegenerative disease, resulting in the loss of self-service and death of the middle-aged and elderly people. In the last 2 decades, significant progress has been made in the study of the pathogenesis of this disease. Two known drugs (riluzole and edaravone) have been approved by the Food and Drug Administration for treatment of amyotrophic lateral sclerosis. The efficacy of these drugs is extremely low, so clinical trials of new drugs are ongoing all over the world. This review discusses the current achievements and future directions of therapy of this disease.

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Causative Genes in Amyotrophic Lateral Sclerosis and Protein Degradation Pathways: a Link to Neurodegeneration

Cited by 55 publications

References 227 publications

Applying Antibodies Inside Cells: Principles and Recent Advances in Neurobiology, Virology and Oncology

Applying Antibodies Inside Cells: Principles and Recent Advances in Neurobiology, Virology and Oncology

Novel Aspects on Motor Neuron Disease: The Recent Genetic Studies on ALS

Amyotrophic lateral sclerosis: pathogenetic mechanisms and new approaches to pharmacotherapy (literature review)

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