Replacing or even eliminating microglia as a therapeutic strategy for AD
seems doable.
http://faculty.sites.uci.edu/kimgreen/b ... thy-brain/
Microglial Therapies for AD?
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progranulindefect
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Re: Microglial Therapies for AD?
https://www.ucsf.edu/news/2016/04/40245 ... l-dementia
"Additional experiments on isolated microglia made it clear to the researchers that progranulin normally acts as a brake to prevent excessive microglia activation. Without it, it appeared that an unknown aspect of the normal aging process allowed microglia to spiral out of control.
However, the researchers showed that they could short-circuit this death spiral by deleting the gene for one of the major complement proteins produced by microglia, called C1qa. Mice with both the progranulin and the C1qa genes turned off lived considerably longer than those with intact C1qa, and didn’t develop OCD-like behaviors. Their brains also showed a drastic reduction in the number of activated microglia and much better protection from synapse loss."
http://www.alzheimers.net/8-22-16-a-new ... s-disease/
"Additional experiments on isolated microglia made it clear to the researchers that progranulin normally acts as a brake to prevent excessive microglia activation. Without it, it appeared that an unknown aspect of the normal aging process allowed microglia to spiral out of control.
However, the researchers showed that they could short-circuit this death spiral by deleting the gene for one of the major complement proteins produced by microglia, called C1qa. Mice with both the progranulin and the C1qa genes turned off lived considerably longer than those with intact C1qa, and didn’t develop OCD-like behaviors. Their brains also showed a drastic reduction in the number of activated microglia and much better protection from synapse loss."
http://www.alzheimers.net/8-22-16-a-new ... s-disease/
Re: Microglial Therapies for AD?
Biology is starting to become interesting!
The underlying assumption has always been that people are largely stuck with whatever body they start out with. My perception is that this assumption is now open to discussion.
Mitochondrial transplantation has now been successfully tested in the clinic. If a world in which mitochondria are easily and routinely translantable were now on the horizon, then a substantial revolution in medicine should be expected. Mitochondria are centrally related to many of the illnesses that we face including AD and cancer.
The website I referenced above mentioned that a chemical exists (PLX3397) that can safely remove microglia from mice. Mice lacking microglia appear healthy. Perhaps at some point in AD progression it would be helpful to likewise remove microglia.
I had not fully understood that microglia are simply the brain's specialized version of macrophages. This being true, one could also conceive of a treatment that eliminated the defective microglia (which is already achievable) and then transplant genetically modified microglia/or GMO stem cells.
Transplanting mitochondria , microglia ... would quickly move us into an entirely new biotech life.
The underlying assumption has always been that people are largely stuck with whatever body they start out with. My perception is that this assumption is now open to discussion.
Mitochondrial transplantation has now been successfully tested in the clinic. If a world in which mitochondria are easily and routinely translantable were now on the horizon, then a substantial revolution in medicine should be expected. Mitochondria are centrally related to many of the illnesses that we face including AD and cancer.
The website I referenced above mentioned that a chemical exists (PLX3397) that can safely remove microglia from mice. Mice lacking microglia appear healthy. Perhaps at some point in AD progression it would be helpful to likewise remove microglia.
I had not fully understood that microglia are simply the brain's specialized version of macrophages. This being true, one could also conceive of a treatment that eliminated the defective microglia (which is already achievable) and then transplant genetically modified microglia/or GMO stem cells.
Transplanting mitochondria , microglia ... would quickly move us into an entirely new biotech life.
Re: Microglial Therapies for AD?
The problem with biology always seems to be that you are never talking from first principles.
Perhaps microglia offers us terra firma to address AD.
Below reference is startling in that it appears to be showing a large range of GWAS hits converge on microglia.
If all that needs to be done is manipulate certain subsets of microglia to prevent neurodegeneration, then this could be feasible.
Anyone checked their rs1057233 genotype?
rs1057233 rs10838698 9475 0.928 1.000 IM,IMD,CYT,OQ,OE,O24,O28,O54,O5E,OEE,AAH chr11 47342499
http://www.alzforum.org/news/research-n ... -age-onset
Perhaps microglia offers us terra firma to address AD.
Below reference is startling in that it appears to be showing a large range of GWAS hits converge on microglia.
If all that needs to be done is manipulate certain subsets of microglia to prevent neurodegeneration, then this could be feasible.
Anyone checked their rs1057233 genotype?
rs1057233 rs10838698 9475 0.928 1.000 IM,IMD,CYT,OQ,OE,O24,O28,O54,O5E,OEE,AAH chr11 47342499
http://www.alzforum.org/news/research-n ... -age-onset
