通过TRPV4介导的Ca2+放松调节会通过多巴胺能神经元中的AKT/α-synuclein通路引起线粒体功能障碍
Xiao Sun1,2,3, Jun Kong1, Shuangshan Dong1
1Section of Oral Medicine for Children, Division of Oral Health, Growth and Development, Faculty of Dental Science Kyushu University Fukuoka Japan.
FASEB bioAdvances
|December 14, 2023
概括
在TRPV4通道中的突变会破坏大脑的水平,导致神经发育问题. 叶酸治疗通过使线粒体功能正常化和改善受影响细胞中神经元健康,显示出有希望的结果.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 干细胞生物学 干细胞生物学
背景情况:
- 暂时受体潜在化物成员4 (TRPV4) 通道调节 (Ca2+).
- TRPV4突变会导致与神经发育相关的疾病.
- 与TRPV4相关的神经发育问题的发病原因和治疗策略尚不清楚.
研究的目的:
- 在神经发育中研究TRPV4介导的放松调节.
- 探索叶酸在TRPV4相关疾病中的治疗潜力.
主要方法:
- 隔离的突变牙髓干细胞具有增益功能TRPV4突变 (c.1855C>T,p.L619F).
- 利用CRISPR/Cas9产生纠正的同源干细胞.
- 将细胞分化为多巴氨基神经元,并检查叶酸的作用.
主要成果:
- 突变神经元表现出较高的细胞质Ca2+和AKT介导的α-syn (α-syn) 诱导.
- 这导致线粒体Ca2+积累和功能障碍.
- TRPV4对抗剂,AKT抑制剂,或α-syn敲击正常化线粒体Ca2+.
- 叶酸通过抑制α-syn转录来使线粒体Ca2+正常化,改善线粒体功能和神经元外生长.
结论:
- 在这些疾病中,TRPV4/Ca2+/AKT诱导的α-syn对于线粒体Ca2+积累至关重要.
- 叶酸通过向α-syn和改善线粒体健康来证明TRPV4相关的神经发育障碍的治疗潜力.
更多相关视频
10:31Three-dimensional Imaging and Analysis of Mitochondria within Human Intraepidermal Nerve Fibers
Published on: September 29, 2017
10.3K
07:32Analyzing Mitochondrial Transport and Morphology in Human Induced Pluripotent Stem Cell-Derived Neurons in Hereditary Spastic Paraplegia
Published on: February 9, 2020
7.8K
相关概念视频
ATP Synthase: Mechanism
14.6K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
14.6K
Neural Regulation
39.5K
Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
39.5K
Parkinson's Disease: Overview
556
Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is...
556
Drugs Affecting Neurotransmitter Synthesis
1.4K
Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase,...
1.4K
Energy to Drive Translocation
2.1K
Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Generally, polypeptides are unfolded by two distinct...
2.1K
Mitochondrial Membranes
10.9K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
10.9K
