相关实验视频

Updated: Jun 23, 2025

Author Spotlight: Generating Neuronal Phenotypic Profiles - A Protocol to Culture and Image Human Midbrain Dopaminergic Neurons

Author Spotlight: Generating Neuronal Phenotypic Profiles - A Protocol to Culture and Image Human Midbrain Dopaminergic Neurons

Published on: July 7, 2023

六胺生物合成途径拯救了帕金森病患者iPSC衍生的中脑神经元中的溶酶体功能障碍

Willayat Y Wani¹, Friederike Zunke^1,2, Nandkishore R Belur¹

¹The Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.

Nature communications

|June 19, 2024

概括

帕金森病涉及破坏葡萄糖代谢和蛋白质错误折叠. 增强赫索胺通路可以恢复蛋白质折叠,并减少大脑中的有毒蛋白质聚合.

科学领域:

神经科学是一个神经科学.
生物化学生物化学
细胞生物学细胞生物学

背景情况:

帕金森病 (PD) 的特点是葡萄糖代谢受损和蛋白质错误折叠.
六胺生物合成途径 (HBP) 对于N-链 glycosylation至关重要,对于蛋白质折叠至关重要.
在PD中,葡萄糖代谢中断与蛋白质错折之间的机制联系尚不清楚.

研究的目的:

为了研究胺生物合成途径在帕金森病中的作用.
探索在PD中葡萄糖代谢,蛋白质折叠和溶酶体功能之间的联系.
确定治疗点,以恢复PD中的蛋白质静止.

主要方法:

在帕金森病患者中脑培养物中分析葡萄糖和尿素-5'-三酸盐水平.
测量N-甘氨酸合成速度的测量.
研究未折叠蛋白质响应 (UPR) 信号及其对赫索胺通路的影响.
对 lysosomal 酶活性和α-synuclein 聚合的评估.

主要成果:

帕金森病患者中脑培养物显示葡萄糖和尿素-5'-三酸盐的增加,N-甘氨酸合成减少.
葡萄糖流量受损与GFPT2酶活性降低有关,由UPR信号干扰介导.
在UPR-HBP信号传递和N-糖化中的失败导致了错误折叠的溶酶体水解酶和α-synuclein积累.
加快HBP葡萄糖流改善了酶功能,并降低了病理性α-synuclein.

结论:

赫索胺途径将葡萄糖代谢与帕金森病中的 lysosomal 功能相结合.
PD涉及UPR-HBP轴的故障,导致蛋白质稳定性受损.
增强赫索胺通路为恢复帕金森病中的蛋白质静止提供了潜在的治疗策略.

更多相关视频

Lentiviral Vector Platform for the Efficient Delivery of Epigenome-editing Tools into Human Induced Pluripotent Stem Cell-derived Disease Models

Lentiviral Vector Platform for the Efficient Delivery of Epigenome-editing Tools into Human Induced Pluripotent Stem Cell-derived Disease Models

Published on: March 29, 2019

Analyzing Mitochondrial Transport and Morphology in Human Induced Pluripotent Stem Cell-Derived Neurons in Hereditary Spastic Paraplegia

Analyzing Mitochondrial Transport and Morphology in Human Induced Pluripotent Stem Cell-Derived Neurons in Hereditary Spastic Paraplegia

Published on: February 9, 2020

相关概念视频

EPS and iPS Cells in Disease Research

EPS and iPS Cells in Disease Research

Embryonic and induced pluripotent stem cells are excellent models for disease research because of their ability to self-renew and differentiate into most cell types. Somatic cells from a patient are isolated and reprogrammed into induced pluripotent stem cells or iPSCs. These iPSCs are later differentiated into the desired cell type, which mirrors the diseased cell of the patient. In this way, disease models have been created for investigating diseases such as Down syndrome, type I diabetes,...

iPS Cell Differentiation

iPS Cell Differentiation

The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.

Lysosomal Hydrolases

Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...