线粒体调节器PGC-1a在神经元代谢和大脑衰老中的作用
Dylan C Souder1, Eric R McGregor1, Timothy W Rhoads2
1Department of Medicine, SMPH, University of Wisconsin Madison, Madison, WI.
bioRxiv : the preprint server for biology
|October 9, 2023
概括
大脑是大脑的大脑.
科学领域:
- 神经科学是一个神经科学.
- 代谢过程中的代谢.
- 衰老的衰老 衰老的衰老
背景情况:
- 大脑需要大量的能量,不同的细胞类型有独特的代谢需求.
- 线粒体功能的关键调节剂PGC-1a在大脑中大量存在,但其在新陈代谢中的细胞特异性作用尚不清楚.
- 衰老影响大脑路径,包括新陈代谢,PGC-1a表达减少.
研究的目的:
- 研究PGC-1a在大脑新陈代谢和适应中的细胞类型特定作用.
- 探索衰老和GSK3b抑制对神经元代谢和PGC-1a活性的影响.
- 阐明大脑衰老和生长网络中的GSK3b/PGC-1a轴.
主要方法:
- 鼠标皮质的转录分析,以评估与年龄相关的变化.
- 蛋白质组分析以确定代谢和核糖体路径的改变.
- 研究神经元和天体细胞PGC-1a对GSK3b抑制的反应 ().
主要成果:
- 衰老会改变免疫,炎症和神经元路径,协调的代谢反应与减少的PGC-1a有关.
- 神经元表达一种专门的PGC-1a异型,在分化和成熟过程中被激活.
- 神经元PGC-1a,但不是星细胞PGC-1a,对GSK3b抑制有反应;治疗大致重编程新陈代谢和生长信号.
结论:
- PGC-1a在大脑的代谢适应中发挥着至关重要的细胞类型特异性作用,特别是在神经元中.
- GSK3b/PGC-1a轴是大脑生长和新陈代谢的核心,影响神经元功能和外长.
- 这个轴与理解和潜在地干预大脑衰老过程非常相关.
相关概念视频
01:37Mitochondria
13.6K
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
13.6K
01:19Regulation of Metabolism
9.5K
Cellular needs and conditions vary from cell to cell and change within individual cells over time. For example, the required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and...
9.5K
01:15Neurogenesis and Regeneration of Nervous Tissue
840
In the CNS, neurogenesis, the birth of new neurons from stem cells, is limited to the hippocampus in adults. In other regions of the brain and spinal cord, neurogenesis is almost non-existent due to inhibitory influences from neuroglia, especially oligodendrocytes, and the absence of growth-stimulating cues. The myelin produced by oligodendrocytes in the CNS inhibits neuronal regeneration. Furthermore, astrocytes proliferate rapidly after neuronal damage, forming scar tissue that physically...
840
01:39Mitochondrial Precursor Proteins
2.6K
Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70 chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
Most of the mitochondrial...
2.6K
02:59Animal Mitochondrial Genetics
7.6K
Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
7.6K