化SARM1参与了罗农诱导的神经退行症的病理过程
Hitoshi Murata1, May Tha Zin Phoo1, Toshiki Ochi1
1Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Journal of biochemistry
|September 19, 2023
概括
无菌α和toll/interleukin受体模式含有蛋白1 (SARM1) 的酸化在帕金森病中升高.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 无菌α和toll/interleukin受体模式含有蛋白1 (SARM1) 是一个关键的NAD+酶,与轴突退化有关.
- c-Jun N-终端酶 (JNK) 通过酸化在Ser-548.8处激活SARM1.
- 在帕金森病 (PD) 病原发生过程中SARM1酸化的作用尚不清楚.
研究的目的:
- 为了研究SARM1酸化在帕金森病 (PD) 病理学中的作用.
- 检查SARM1激活及其对PD模型中神经退行症的贡献.
主要方法:
- 利用罗农诱导PD类病态诱导诱导多能干细胞 (iPSC) 衍生神经元从健康的捐赠者和患有家族PD PARK2 (FPD2) 的患者.
- 在PD模型中评估SARM1酸化水平和神经元对压力的脆弱性.
- 采用JNK抑制剂,Ca2+信号抑制剂,SARM1敲击和SARM1突变过度表达 (S548A) 来调节SARM1的活动.
- 在PD模型小鼠中脑中检查了SARM1酸化.
主要成果:
- 与健康对照人群相比,FPD2神经元和PARK2敲击神经元对罗诺诱导的压力和较高的SARM1酸化的脆弱性增加.
- 在PD模型神经元中,JNK抑制剂,Ca2+信号抑制剂和SARM1敲击减轻了退行性事件.
- 野生型SARM1的过度表达增强了退化,而SARM1-S548A突变抑制了它.
- 在PD模型小鼠的中脑中观察到高SARM1酸化.
结论:
- 化SARM1在罗诺诱导的神经退行症的病理过程中发挥着重要作用.
- 准SARM1酸化或其上游激活剂,如JNK,可能为帕金森病提供治疗策略.
关键词:
在JNK中,JNK就是JNK.在PARK2中.帕金森病是帕金森氏症的一种疾病.酸化是指酸化的方法.简称:ARM, armadillo/HEAT motif; DMSO, dimethyl sulfoxide; EGTA, ethylene glycol-bis(2-aminoethelether) -N:N:N:N:N-四酸; iPSC,诱导多能干细胞; JNK,c-Jun N-终端激酶; NAD,尼古丁胺二核酸; NSC,神经干细胞; NF-L,神经纤维-L; NF-M,神经纤维-M; PD,斯病; PINK1,PTEN诱导的激酶1; ROS,活性氧物种; SAM,无菌α; SARM1,无菌α和T/interleukin受体含蛋白质的动机; SNpc1; SNpc1; nigragra; TH; TH; tyrosine hydroxylase; TIR/T; TIR; WIR; 野生类型的受体;更多相关视频
11:53Oral Administration of Rotenone using a Gavage and Image Analysis of Alpha-synuclein Inclusions in the Enteric Nervous System
Published on: October 26, 2010
17.1K
09:02Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing
Published on: June 9, 2017
23.3K
相关概念视频
Phosphorylation
50.5K
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
50.5K
Protein Kinases and Phosphatases
13.2K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
13.2K
PI3K/mTOR/AKT Signaling Pathway
3.6K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.6K
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
