-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
Written | Qi is similar to other organs.
The proliferative activity of neural stem cells (NSCs) in the mammalian brain decreases with age.
In the past ten years, some molecular factors that mediate the process of age-related neurogenesis loss have been identified.
Among them, Lamins, in addition to the function of anchoring chromatin around the nucleus, is considered to be the internal mediator of cell aging.
At present, it has been found that Lamin A (LA) mutations encoded by LMNA are causally related to the occurrence of Hutchinson-Gilford Progeria Syndrome (HGPS) by disrupting nuclear shape and function.
These LMNA mutations lead to the LA truncated body called "progerin".
Expression subsequently leads to an increase in the level of the nuclear membrane protein SUN1, and the up-regulation of SUN1 protein seems to be a key event in the detrimental effect of LMNA mutation on cell function.
Interestingly, the ectopic expression of progerin in hippocampal neural stem cells disrupted the function of the diffusion barrier in the endoplasmic reticulum (ER) membrane, resulting in the inability to properly separate aging factors.
In addition, some findings indicate that during mammalian cell division, lamin is integrated into the endoplasmic reticulum membrane together with other components of the nuclear membrane, and may be involved in regulating the strength of the endoplasmic reticulum diffusion barrier and cell division.
Combined with the data on the high expression of Lamin B1 (LB1) in hippocampal neural stem cells, can it be inferred that changes in LB1 levels may lead to age-dependent changes in hippocampal neural stem cell activity? Not long ago, the Sebastian Jessberger team from the University of Zurich in Switzerland and the Darcie L.
Moore team from the University of Wisconsin in the United States published an article entitled Declining lamin B1 expression mediates age-dependent decreases of hippocampal stem cell activity in the Cell Stem Cell magazine.
This short article reveals the intrinsic regulatory mechanism of the age-dependent changes in hippocampal neural stem cell activity mediated by lamin B1, and shows that selective overexpression of LB1 in the neurogenic lineage is sufficient to enhance neurogenesis in vivo and save the elderly neural stem cells.
Proliferation defects.
Based on the previous findings, the authors first analyzed the changes in the levels of related proteins in the hippocampus of 6-week-old and 9-month-old mice.
It can be clearly observed that the LB1 protein level in aging neural stem cells is reduced, while the SUN1 protein level is increased.
So is there a regulatory relationship between these two proteins with diametrically opposite reactions? If overexpression of LB1 in elderly neural stem cells can effectively reduce the level of SUN1, on the contrary, knocking down SUN1 with shRNA will not change the protein level of LB1, suggesting that the regulation of LB1 and SUN1 is unidirectional in hippocampal neural stem cells.
The establishment of a diffusion barrier in the endoplasmic reticulum membrane contributes to the separation of aging factors in proliferative NSCs, and the strength of the barrier in NSCs also shows age-related changes.
By labeling the fluorescence loss of GFP protein in the ER membrane or ER cavity in the photobleaching experiment, the authors observed that overexpression of LB1 in old neural stem cells or down-regulation of SUN1 protein based on shRNA can repair the barrier strength, while LB1 in young neural stem cells is missing Or SUN1 overexpression does not affect the strength of the endoplasmic reticulum barrier.
Next, the author wants to know whether LB1 can save the proliferation ability of elderly neural stem cells and neurogenesis in the hippocampus.
EdU pulse labeling and cell cycle analysis gave consistent results as expected, that is, LB1 overexpression can restore the proliferation ability of progenitor cells.
Subsequently, the author used a tissue-specific method to selectively enhance the expression of LB1 in adult neural stem cells and their progeny.
Two days after stereotactic injection of floxed-LB1-CFP or control floxed-CFP virus into the hippocampus of Gli1/tdTomato mice, Tam was injected Activation of Cre-dependent LB1 expression leads to increased proliferation and neurogenesis of target neuronal cells (yellow fluorescence), and correspondingly, the protein level of SUN1 in yellow fluorescent cells decreases.
In summary, this study showed that LB1 and SUN1 are dynamically regulated in hippocampal neural stem cells with age, and identified a new mechanism, that is, how age-mediated intracellular molecular changes affect stem cell behavior in adult mammalian brains .
However, the above is only a rough study.
How LB1 and SUN1 affect each developmental stage from resting stem cells to mature neurons needs to be further analyzed in future research.
Original link: https://doi.
org/10.
1016/j.
stem.
2021.
01.
015 Plate maker: November
The proliferative activity of neural stem cells (NSCs) in the mammalian brain decreases with age.
In the past ten years, some molecular factors that mediate the process of age-related neurogenesis loss have been identified.
Among them, Lamins, in addition to the function of anchoring chromatin around the nucleus, is considered to be the internal mediator of cell aging.
At present, it has been found that Lamin A (LA) mutations encoded by LMNA are causally related to the occurrence of Hutchinson-Gilford Progeria Syndrome (HGPS) by disrupting nuclear shape and function.
These LMNA mutations lead to the LA truncated body called "progerin".
Expression subsequently leads to an increase in the level of the nuclear membrane protein SUN1, and the up-regulation of SUN1 protein seems to be a key event in the detrimental effect of LMNA mutation on cell function.
Interestingly, the ectopic expression of progerin in hippocampal neural stem cells disrupted the function of the diffusion barrier in the endoplasmic reticulum (ER) membrane, resulting in the inability to properly separate aging factors.
In addition, some findings indicate that during mammalian cell division, lamin is integrated into the endoplasmic reticulum membrane together with other components of the nuclear membrane, and may be involved in regulating the strength of the endoplasmic reticulum diffusion barrier and cell division.
Combined with the data on the high expression of Lamin B1 (LB1) in hippocampal neural stem cells, can it be inferred that changes in LB1 levels may lead to age-dependent changes in hippocampal neural stem cell activity? Not long ago, the Sebastian Jessberger team from the University of Zurich in Switzerland and the Darcie L.
Moore team from the University of Wisconsin in the United States published an article entitled Declining lamin B1 expression mediates age-dependent decreases of hippocampal stem cell activity in the Cell Stem Cell magazine.
This short article reveals the intrinsic regulatory mechanism of the age-dependent changes in hippocampal neural stem cell activity mediated by lamin B1, and shows that selective overexpression of LB1 in the neurogenic lineage is sufficient to enhance neurogenesis in vivo and save the elderly neural stem cells.
Proliferation defects.
Based on the previous findings, the authors first analyzed the changes in the levels of related proteins in the hippocampus of 6-week-old and 9-month-old mice.
It can be clearly observed that the LB1 protein level in aging neural stem cells is reduced, while the SUN1 protein level is increased.
So is there a regulatory relationship between these two proteins with diametrically opposite reactions? If overexpression of LB1 in elderly neural stem cells can effectively reduce the level of SUN1, on the contrary, knocking down SUN1 with shRNA will not change the protein level of LB1, suggesting that the regulation of LB1 and SUN1 is unidirectional in hippocampal neural stem cells.
The establishment of a diffusion barrier in the endoplasmic reticulum membrane contributes to the separation of aging factors in proliferative NSCs, and the strength of the barrier in NSCs also shows age-related changes.
By labeling the fluorescence loss of GFP protein in the ER membrane or ER cavity in the photobleaching experiment, the authors observed that overexpression of LB1 in old neural stem cells or down-regulation of SUN1 protein based on shRNA can repair the barrier strength, while LB1 in young neural stem cells is missing Or SUN1 overexpression does not affect the strength of the endoplasmic reticulum barrier.
Next, the author wants to know whether LB1 can save the proliferation ability of elderly neural stem cells and neurogenesis in the hippocampus.
EdU pulse labeling and cell cycle analysis gave consistent results as expected, that is, LB1 overexpression can restore the proliferation ability of progenitor cells.
Subsequently, the author used a tissue-specific method to selectively enhance the expression of LB1 in adult neural stem cells and their progeny.
Two days after stereotactic injection of floxed-LB1-CFP or control floxed-CFP virus into the hippocampus of Gli1/tdTomato mice, Tam was injected Activation of Cre-dependent LB1 expression leads to increased proliferation and neurogenesis of target neuronal cells (yellow fluorescence), and correspondingly, the protein level of SUN1 in yellow fluorescent cells decreases.
In summary, this study showed that LB1 and SUN1 are dynamically regulated in hippocampal neural stem cells with age, and identified a new mechanism, that is, how age-mediated intracellular molecular changes affect stem cell behavior in adult mammalian brains .
However, the above is only a rough study.
How LB1 and SUN1 affect each developmental stage from resting stem cells to mature neurons needs to be further analyzed in future research.
Original link: https://doi.
org/10.
1016/j.
stem.
2021.
01.
015 Plate maker: November
