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基于干细胞的帕金森病建模方案。

Stem Cell-Based Modeling Protocol for Parkinson's Disease.

机构信息

Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Iranian Cancer Control Center (MACSA), Tehran, Iran.

出版信息

Methods Mol Biol. 2024;2736:105-114. doi: 10.1007/7651_2022_473.

Abstract

Parkinson's disease is a progressive neurodegenerative disorder, which is mainly characterized by unintended or uncontrollable body movements. Pathophysiologically, disturbances in the neurotransmission system of the brain like dopaminergic system and synaptic dysfunction are classified as top-rated causes of the onset of Parkinson's disease, which symptoms can be different according to the involvement of neurotransmission system type and the effect of the disease on the motor and non-motor systems. Although some pharmacological and non-pharmacological approaches have been applied to control and slow down the progression of the disease, a definitive cure has not yet been discovered. One of the factors involved in this issue is the lack of appropriate laboratory models to investigate the pathological mechanisms involved in the disease as well as various aspects of candidate drugs, which ultimately leads to the failure of drug discovery and development pipelines. To deal with these challenges, the application of stem cells, especially cellular reprogramming of somatic cells to human pluripotent stem cells, also known as induced pluripotent stem cells, has been able to promise a new chapter in the modeling of Parkinson's disease. Induced pluripotent stem cells have the stemness capability; therefore, they can differentiate into any type of cell such as nerve cells. Also, since these cells are obtained from the reprogramming of somatic cells in the patient's body, they maintain the patient's genetic content, which can play an important role in increasing the quality of disease modeling and the validity of the results of laboratory studies. Therefore, the procedure for modeling induced pluripotent stem cells for Parkinson's disease is explained in this chapter.

摘要

帕金森病是一种进行性神经退行性疾病,主要表现为无意识或无法控制的身体运动。从病理生理学角度来看,大脑神经递质系统(如多巴胺能系统)紊乱和突触功能障碍等被认为是帕金森病发病的主要原因,其症状根据涉及的神经递质系统类型和疾病对运动和非运动系统的影响而有所不同。尽管已经应用了一些药理学和非药理学方法来控制和减缓疾病的进展,但仍未发现明确的治愈方法。导致这一问题的因素之一是缺乏适当的实验室模型来研究疾病相关的病理机制以及候选药物的各个方面,这最终导致药物发现和开发管道的失败。为了应对这些挑战,干细胞的应用,特别是体细胞向人类多能干细胞的细胞重编程,也称为诱导多能干细胞,有望为帕金森病的建模开辟新篇章。诱导多能干细胞具有干细胞特性;因此,它们可以分化为任何类型的细胞,如神经细胞。此外,由于这些细胞是从患者体内体细胞的重编程中获得的,因此它们保留了患者的遗传物质,这在提高疾病建模的质量和实验室研究结果的有效性方面发挥着重要作用。因此,本章介绍了用于帕金森病建模的诱导多能干细胞的程序。

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