Nerve cell damage and apoptosis are closely related to neurodegenerative diseases, but the mechanism is unclear. The "killing" of neurons by astrocytes (astrocyte) under inflammation is considered to be an important mechanism, but the specific "killing" method is unknown (1, 2).
Shane Liddelow of New York University School of Medicine and Stanford University Ben Barres and other researchers used mass spectrometry and other methods to analyze the killing of activated astrocytes to surrounding sensitive cells (oligodendrocytes are mainly used in this article) The "weapon" discovery: astrocytes kill cells not mainly through proteins, but mainly through lipid substances; in mice, astrocytes specifically knock out the enzyme (Elovl1) that synthesizes saturated long-chain free fatty acids. ) can alleviate astrocyte damage to nerve cells and oligodendrocytes in vivo and in vitro (3).
Astrocytes mainly kill cells through lipid substances (3)
Astrocyte-specific knockout of Elovl1 can alleviate the damage of nerve cells and oligodendrocytes (3)
The researchers believe that further research is needed The mechanism of astrocyte activation and saturated long-chain free fatty acid damage to neurons and other cells (or is it related to lipid droplets ?) , so as to find suitable targets for intervention and alleviate physiological and pathological nervous system Degenerate (3).
This work was published in nature on October 6, 2021.
Comments:
Further direct evidence is needed for the cytotoxicity mediated by "harmful" lipid substances in the body (such as accumulation of lipid substances in the body, etc.);
In addition, mutations in key fatty acid metabolism enzymes in the population are associated with neurodegeneration. The connection between diseases deserves further analysis;
In addition, why astrocytes kill surrounding cells through lipid substances and its selective killing mechanism (mainly killing nerve cells and oligodendrocytes) are also key issues.
https://www.nature.com/articles/s41586-021-03960-y
Corresponding author introduction:
https://www.liddelowlab.com/shane-liddelow
https://www.nature.com/articles/d41586-017 -08964-1
Reference:
1. S. A. Liddelow, B. A. Barres, Reactive Astrocytes: Production, Function, and Therapeutic Potential. Immunity. 46,957–967 (2017).
2. S. A. Liddelow et al., Neurotoxic reactive astr cells are induced by activated microglia. Nature.541, 481–487 (2017).
3. K. A. Guttenplan et al., Neurotoxic reactive astrocytes induce cell death via saturated lipids. Nature, 1–6 (2021).
Original link:
https://www. nature.com/articles/s41586-021-03960-y
