How Knowledge Of Neurons Has Allowed Illnesses - amazonia.fiocruz.br

How Knowledge Of Neurons Has Allowed Illnesses - apologise

Background: Alzheimer's disease AD is the most common type of dementia, affecting one in eight adults over 65 years of age. In the present study, our aim was to establish an in vitro cell model based on patient-specific human neurons to study the pathomechanism of sporadic AD. Methods: We compared neurons derived from induced pluripotent stem cell iPSC lines of patients with early-onset familial Alzheimer's disease fAD , all caused by mutations in the PSEN1 gene; patients with late-onset sporadic Alzheimer's disease sAD ; and three control individuals without dementia. Results: Neurons from patients with fAD and patients with sAD showed increased phosphorylation of TAU protein at all investigated phosphorylation sites. Moreover, elevated sensitivity to oxidative stress, as induced by amyloid oligomers or peroxide, was detected in both fAD- and sAD-derived neurons. Our findings demonstrate that iPSC technology is suitable to model both fAD and sAD and may provide a platform for developing new treatment strategies for these conditions. How Knowledge Of Neurons Has Allowed Illnesses.

How Knowledge Of Neurons Has Allowed Illnesses Video

What is motor neurone disease (MND)?

A reliable disease model is critical to the study of specific disease mechanisms as well as for the discovery and development of new drugs. Despite providing crucial see more into the mechanisms of neurodegenerative diseases, translation of this information to develop therapeutics in clinical trials have been unsuccessful. Reprogramming technology to convert adult somatic cells to induced Pluripotent Stem Cells iPSCs or directly reprogramming adult somatic cells to induced Neurons iNhas allowed for the creation of better models to understand the molecular mechanisms How Knowledge Of Neurons Has Allowed Illnesses design of new drugs. In recent times, iPSC technology has been commonly used for modeling neurodegenerative diseases and drug discovery. However, several technological challenges have limited the application of iN.

As evidence suggests, iN for the modeling of neurodegenerative disorders is advantageous compared to those derived from iPSCs. In this review, we will compare iPSCs and iN models for neurodegenerative diseases and their potential applications in the future.

Introduction

Neurodegenerative diseases comprised of a group of complicated disorders of the central nervous system among the aged population. To design effective treatment strategies to cure these diseases, scientists are in desperate need of convenient and reliable disease models. Previous neurodegenerative disease models based on genetic manipulations include transgene integration or gene knockout systems. These systems can only be utilized partially to understand disease mechanisms, How Knowledge Of Neurons Has Allowed Illnesses, and progression Hargus et al. These current models cannot be used as accurate models for neurodegenerative diseases especially due to specific limitations. First, although the fibroblasts or disease-associated mutation transformed cell lines of patients have enabled detailed mechanistic studies to be carried out, the biology of cell lines does not resemble the biology of primary neurons Hargus et al.

Second, animal models-such as dogs, flies, monkeys, and especially rodents Zhao et al. However, these models often cannot accurately recapitulate human disease and animal models of the sporadic learn more here of neurodegenerative diseases due to species-specific differences. In addition, it is difficult to manipulate affected cell types in neurodegenerative disorders in vitro. Due to these link, a number of preclinical trials that aimed to identify drugs have failed to successfully translate into therapeutics in clinical settings Kraljevic et al.

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In summary, it is important to develop accurate and predictive disease models as they are essential Hw providing key insights to understanding disease mechanisms and the development of drugs to cure neurodegenerative diseases. Innovations in cellular reprogramming technology have provided us with a promising tool to solve this problem. Takahashi and Yamanaka established a unique method of reprogramming somatic cells to iPSCs, which can be differentiated into cell types of all the three germ layers including non-proliferating neurons.

The neurons derived from iPSCs would have the same genetic information as the individual patient and can be differentiated from iPSCs. This technology has been utilized by other investigators for neurodegenerative disease modeling Table 1 ; Wan et al. Moreover, in recent years, the discovery of direct reprogramming technology has enabled the reprogramming of somatic cells to neurons, bypassing the iPSC stage Vierbuchen et al. With the advancement of these technologies, scientists have been able to create highly efficient and lineage-specific neurons through the reprogramming of somatic cells Marro et al. Altogether, these technologies can be used for modeling neurodegenerative diseases Shi et al.

Among them, recent studies have indicated that the application of iN for aging-related neurodegenerative diseases would be a better choice, Illneses it does not reset aging information Mertens et al. In this review, we summarize recent studies involving iPSCs and in neurodegenerative Knowlerge modeling and its advantages and limitations. Ina phenomenal study conducted in Yamanaka lab demonstrated that viral vectors carrying a combination of pluripotent transcription factors, including Oct4, Sox2, Klf4, and c-Myc OSKMwere sufficient to effectively reprogram mouse How Knowledge Of Neurons Has Allowed Illnesses cells to iPSCs Takahashi and Yamanaka, read article Okano and Yamanaka, The generated iPSCs had the potential to be differentiated into all three germ layers of cell type with the unlimited ability of self-renewal.

In addition, this technology has been successfully used for translating into other somatic cell types, such as neural stem cells Eminli et al. However, the current iPSC technology still has some limitations, including low efficiency and a long reprogramming process, which are primarily due to the existence of several roadblocks Ebrahimi, ; Haridhasapavalan et al.

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Another problem is that iPSCs may cause cancerous tumor formation due to an undifferentiated pluripotent stem cell after transplantation Choi and Hong, Maherali et al. This system could even reprogram keratinocytes into iPSCs within 10 days Maherali et al.

In addition, using lentivirus or retrovirus to deliver OSKM may cause insertional mutagenesis when integrating gene sequences in the genomic DNA of the cells. To improve technical safety, other delivery methods, including non-viral or non-integrating viral vectors, have been attempted, such as protein transduction, the transfection of modified mRNA transcripts, small molecules, sendai virus, and episomal vectors Sommer and Mostoslavsky,; Gonzalez et al.]