|
|
Joined: 12/20/2011
Posts: 217
|
Young blood can reverse some effects of ageing,
study finds
Blood from young mice improved learning and memory in
older mice, and increased connections between their brain cells
Wednesday 17 October 2012
It is rumoured that the late Kim Jong-il would inject himself with blood from healthy young virgins in a bid to slow the ageing process. Remarkably, the North Korean dictator might have been onto something. Experiments on mice have shown that it is possible to rejuvenate the brains of old animals by injecting them with blood from the young.
Saul Villeda of Stanford University, who led the work, found that blood from
young mice reversed some of the effects of ageing in the older mice, improving
learning and memory to a level comparable with much younger animals. He said
that the technique could one day help people stave off the worst effects of
ageing, including conditions such as Alzheimer's.
"Do I think that giving young blood could have an effect on a human? I'm
thinking more and more that it might," said Villeda. "I did not, for sure, three
years ago."
He presented his results at the annual meeting of the Society for Neuroscience in New Orleans on Wednesday.
Villeda connected the circulatory systems of an old and young mouse so that
their blood could mingle. This is a well-established technique used by
scientists to study the immune system called heterochronic parabiosis. When he
examined the old mouse after several days, he found several clear signs that the
ageing process had slowed down.
The number of stem cells in the brain, for example, had increased. More
important, he found a 20% increase in connections between brain cells. "One of
the main things that changes with ageing are these connections, there are a lot
less of them as we get older," said Villeda. "That is thought to underlie memory
impairment – if you have less connections, neurons aren't communicating, all of
a sudden you have [problems] in learning and memory."
The work builds on a paper published last year in Nature where Villeda and his colleagues at the Stanford University School of Medicine found that the brains of young mice began to age more rapidly when exposed to blood from an older mouse. The number of stem cells in the older mice's brains also increased after receiving blood from the younger mice.
In the latest study, which has not yet been published in a peer-reviewed
journal, Villeda also tested the behaviour of the rejuvenated mice. He took
blood plasma – the fluid portion of blood that is not cells – from two-month-old
mice and injected small amounts, around 5% of the total amount of blood in a
mouse by volume, into 18-month-old animals eight times over the course of a
month.
When he put the animals into a water maze, a test where they have to remember
the location of a hidden platform, he found that the older mice did almost as
well as mice of 4-6 months old. Untreated older mice would make many errors and
swim down blind alleys in their attempts to find the hidden platform, whereas
the mice that had received plasma from young mice located the platform first
time, in most cases.
Villeda said that the young blood most likely reversed ageing by topping up
levels of key chemical factors that tend to decline in the blood as animals age.
Reintroduce these and "all of a sudden you have all of these plasticity and
learning and memory-related genes that are coming back". Which factors in
particular are causing the effect is unclear since there are hundreds of
thousands in blood.
Turning the idea into a therapy for humans will take much more research, but
Villeda said there was no reason not to think that, at some point in the future,
people in their 40s or 50s could take therapies based on the rejuvenating
chemical factors in younger people's blood, as a preventative against the
degenerative effects of ageing.
Andrew Randall, a professor in applied neurophysiology at Exeter and Bristol Universities, said that the brain and other organs inevitably deteriorate as part of the ageing process. "Although this [research] may suggest that Bram Stoker had ideas way ahead of his time, temporarily plumbing teenagers' blood supplies into those of their great-grandparents does not seem a particularly feasible future therapy for
cognitive decline in ageing. Instead this fascinating work suggests there may be
significant benefit in working out what the 'good stuff' is in the high octane
young blood, so that we can provide just those key components to the
elderly."
Chris Mason, professor of regenerative medicine bioprocessing at University
College London, said that real scientific breakthroughs "are often the result of
an astonishing observation that if robustly examined may occasionally contain a
nugget of great value. This may be one such occasion. The important questions
are: what is in the blood of the younger mice that impacts the ageing process,
and is it applicable to humans? Neither will be easy questions to answer."
He added: "Even if the finding leads only to a drug that prevents, rather
than reverses the normal effects of ageing on the brain, the impact upon future
generations will be substantial – potentially outweighing other wonder drugs
such as penicillin."
http://www.guardian.co.uk/science/2012/oct/17/young-blood-reverse-effects-ageing?CMP=twt_fd
|
|
Joined: 12/20/2011
Posts: 217
|
... One question raised by the findings: What about an older patient who receives
a blood transfusion from a younger person?
Would he experience a boost in mental abilities, similar to going back 40 or 50 years in a time machine?
"A clinician at a recent conference told me there are case reports of people
showing cognitive improvement after receiving blood transfusions for unrelated conditions," shares Wyss-Coray.
Though the notion might seem far-fetched, could
future therapies—say, for early Alzheimer's disease—be based on blood-switching
techniques?
Wyss-Coray says, "I do think it's possible we would see a benefit,
but I wouldn't want to raise hopes for this now."...
Much more here:
http://www.research.va.gov/currents/sept11/sept11-04.cfm
|
|
Joined: 12/9/2011
Posts: 13599
|
Not published in a Peer Reviewed Journal as yet, not validated as yet, will be interesting to see if this goes anywhere.
|
|
Joined: 11/29/2011
Posts: 7027
|
And I don't get excited about animal studies. Too many times, the transfer has not led anywhere.
It certainly sounds like science fiction.
|
|
Joined: 12/20/2011
Posts: 217
|
Johanna and Mimi, thanks for your comments. Yes, it's wise to be cautious.
You're right that the Guardian article says that the study hadn't yet been published in a peer-reviewed journal. But now it has.
More details about the study are given in the posts below...
|
|
Joined: 12/20/2011
Posts: 217
|
NIH Public Access
Author manuscript
Accepted for publication in a peer reviewed journal
Nature. Author manuscript; available in PMC 2012 March 1.
Published in final edited form as:
The aging systemic milieu negatively regulates neurogenesis and cognitive
function
Summary
In the central nervous system (CNS), aging results in a precipitous
decline in adult neural stem/progenitor cells (NPCs) and neurogenesis, with
concomitant impairments in cognitive functions1.
Interestingly, such impairments can be ameliorated through systemic perturbations such as exercise1.
Here, using heterochronic parabiosis we show that blood-borne factors present in the systemic milieu can inhibit or promote adult neurogenesis in an age dependent fashion in mice.
Accordingly, exposing a young animal to an old systemic environment, or to plasma from old mice,
decreased synaptic plasticity and impaired contextual fear conditioning and
spatial learning and memory.
We identify chemokines - including CCL11/Eotaxin –
whose plasma levels correlate with reduced neurogenesis in heterochronic
parabionts and aged mice, and whose levels are increased in plasma and cerebral
spinal fluid of healthy aging humans.
Finally, increasing peripheral CCL11
chemokine levels in vivo in young mice decreased adult neurogenesis and impaired
learning and memory.
Together our data indicate that the decline in
neurogenesis, and cognitive impairments, observed during aging can be in part
attributed to changes in blood-borne factors.
See the full paper here:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170097/
This version includes charts & graphs etc.:
http://ukpmc.ac.uk/articles/PMC3170097/reload=0;jsessionid=VgTVUF0cMmXMRPRGAMkv.4
|
|
Joined: 12/20/2011
Posts: 217
|
Here's a page with links to some reactions
and comments on the study:
http://www.stanford.edu/group/twclab/cgi-bin/index.php?option=com_content&view=article&id=49:nature-publication&catid=1:research
________________________________________________
Here, for example, is a comment from the Alzheimer Research Forum:
Paper Alert: Do Blood-Borne Factors Control Brain Aging?
31 August 2011.
Today in Nature, researchers led by Tony Wyss-Coray at Stanford
University, Palo Alto, California, confirm what has been playfully called the
“vampire principle”:
Young blood rejuvenates older mice, while old blood
contains factors that age the brains of young mice, suppressing neurogenesis.
First author Saul Villeda previously presented the bulk of these data at the
2009 Society for Neuroscience annual conference (see ARF related conference
story).
Villeda and colleagues reached this conclusion via parabiosis experiments in
which they sutured the abdominal lining of a young mouse to that of an older
mouse. The capillary beds fused, allowing the mice to exchange blood for two
months. While neurogenesis in the dentate gyrus dropped in young mice subjected
to the procedure, neuron production boomed threefold in the old mice.
The researchers traced the neuron bust in young mice to blood-borne factors from the older animals—in particular, the chemokine eotaxin (also known as CCL11), which plays a role in allergic responses. Plasma CCL11 increases with age in both mice and humans, the researchers found. Systemically injecting eotaxin alone into
young mice inhibited neurogenesis, confirming its central role.
The paper correlates these neurogenesis effects to deficits in learning and
memory.
Young mice who received either old blood or systemic eotaxin injections
showed less long-term potentiation in the dentate gyrus than normal young mice,
and also learned poorly in the water maze and in fear conditioning tests. The
learning problems matched those of young mice whose neural stem cells had been
ablated by radiation, suggesting that the lack of new neurons might be to blame
for memory problems.
But exactly how eotaxin causes these deficits is unclear.
One question is whether it can directly affect the brain, or whether it acts
through other plasma factors.
To get at this question, the researchers injected
eotaxin directly into the dentate gyrus, and again saw a dampening of
neurogenesis.
Importantly, when the researchers also injected an
eotaxin-neutralizing antibody, neurogenesis remained high. The results suggest
that the factor might act directly in the brain.
In an accompanying editorial, Richard Ransohoff at the Cleveland Clinic,
Ohio, notes these data suggest that “factors that alter neurogenesis, such as
exercise or systemic inflammation, might act by modifying the abundance of
signaling proteins in the blood plasma.”
It is not clear if eotaxin acts directly on stem cells, Ransohoff points out, as its receptor, CCR3, is not typically found on stem and progenitor cells. Ransohoff speculates that eotaxin could be acting on microglia, which are known to dampen neurogenesis under some conditions, or it might be suppressing interleukin-4, which normally acts to restrain brain inflammation that might otherwise impair neurogenesis.
Though the mechanisms remain to be determined, “the good news from this report is that neural stem cells in the aging brain do not undergo irreversible decline and can respond to a favourable environment,” Ransohoff wrote.
—Madolyn Bowman Rogers.
References:
Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri
G, Stan TM, Fainberg N, Ding Z, Eggel A, Lucin KM, Czirr E, Park JS,
Couillard-Després S, Aigner L, Li G, Peskind ER, Kaye JA, Quinn JF, Galasko DR,
Xie XS, Rando TA, Wyss-Coray T.
The ageing systemic milieu negatively regulates
neurogenesis and cognitive function.
Nature. 2011 Aug 31. Abstract
Ransohoff RM. Blood ties. Nature. 2011 Aug 31. Abstract
http://www.alzforum.org/new/detail.asp?id=2885
|
|
Joined: 12/20/2011
Posts: 217
|
Here's a very interesting comment posted in the Alzheimer Research Forum:
Comment by: Carol Delany
Submitted 6 September 2011
Permalink
Posted 7 September 2011
Just an observation: My
86-year-old father with Alzheimer's onset in 2006 had a gastrointestinal bleed
and received 11 units of packed cells. After the first six units, his short-term
memory improved significantly. He was able to read news articles and explain
them 30 minutes later. Remembered visitors and their conversations. Did not
repeat himself or ask the same questions repeatedly. Now at three weeks out from
the last transfusion and no active bleeding, the short-term memory has returned
to baseline, i.e., very poor. Coincidence, maybe, but it was nice to have "real"
Dad back for a while.
http://www.alzforum.org/new/detail.asp?id=2885
|
|
Joined: 4/24/2012
Posts: 484
|
Wow. This is very interesting, thanks onward. This is similar to the Gammaguard treatment that uses refined blood plasma containing naturally occurring antibodies.
http://www.ingentaconnect.com/content/adis/dgs/2010/00000070/00000005/art00001
Is the blood factor eotaxin (also known as CCL11) which seems to be the beneficial component in blood also in Gammaguard? I'm thinking it is probably removed. However, the blood infusion would contain all components that are in Gammaguard only not as concentrated.
Also, interesting that in the anecdotal case above, all improvements in memory were lost in just three weeks after discontinuing transfusions.
|
|
Joined: 12/20/2011
Posts: 217
|
Serenoa, thanks. Sorry I don't know enough to answer your question about Gammagard.
If I understand right, eotaxin (also known as CCL11) inhibits neurogenesis (the birth or development of neurons). So eotaxin/CCL11 is causing problems, but components in young blood can overcome that.
Quoting from the article in the Alzheimer Research Forum: "Plasma CCL11 increases with age in both mice and humans, the researchers found. Systemically injecting eotaxin alone into young mice inhibited neurogenesis, confirming its central role. The paper correlates these neurogenesis effects to deficits in learning and memory."
http://www.alzforum.org/new/detail.asp?id=2885
___________________________________________________
If I understand right, the researchers are trying to identify the components in young blood that stimulate the growth of new brain cells.
Then maybe it could be taken in pill form to reverse cognitive decline in the elderly.
Here's an article from the science section of the Guardian that explains what the researchers are hoping to do.
Young blood rejuvenates old brains
The blood of young mice contains proteins that promote growth of new brain cells
by Mo Costandi
Posted on Monday 5
September 2011 10.04 EDT guardian.co.uk
Rejuvenating factors in young blood could alleviate the decline in cognitive
function that comes with old age.
A decline in cognitive function is a normal consequence of ageing. Most of us
begin to experience mild memory loss as we get older. The speed at which the
brain processes information also slows down, and reasoning ability becomes
impaired. For reasons that are still unclear, the rate of this decline is
accelerated in some, and these people go on to develop Alzheimer's disease or
some other form of dementia.
Imagine taking a pill
that could slow down or reverse this age-related decline in cognitive function.
That may one day be possible, if the results of a new study are to be believed.
The new research, published in the current issue of the journal Nature,
shows that the blood of young mice contains as yet unidentified proteins that
can promote the generation of new brain cells in old mice.
We now know
that the mammalian brain contains neural stem cells that continue
to generate new cells throughout adulthood. The discovery of this process –
adult neurogenesis – is perhaps the most significant finding of modern neuroscience, as it
overturned the long-held view that the adult brain is incapable of regenerating
itself and opened up the possibility of developing stem cell-based therapies for
neurological conditions such as stroke and Parkinson's disease.
New brain cells are generated by the division of stem cells found in two
discrete regions of the brain. One of these regions, the subventricular zone,
generates cells that migrate to the olfactory bulb; the other, called the
subgranular zone, produces cells that migrate into the hippocampus, a brain
structure known to be critical for learning and memory formation. Newborn cells
contribute to these functions, and it is likely that age-related cognitive
decline is related to a reduction in the rate at which new cells are
produced.
Earlier work has shown
that the neural stem cells are located close to
blood vessels. This prompted Tony Wyss-Coray of
Stanford University and his colleagues to investigate the possibility that
neurogenesis may be regulated by chemical cues delivered to the brain in the
blood. To do so, they performed surgery to create artificial Siamese twin mice,
allowing for the exchange of blood between each pair of animals. They created
three different types of twins: young adult mice joined to each other, old mice
joined to each other and young mice joined to old mice.
The researchers killed the animals five weeks after the surgery and analysed
their brains to determine the number of newly generated cells. This is done by
injecting a synthetic chemical called 5-bromo-2'deoxyuridine (BrdU), which
resembles one of the four main chemical components of DNA, and is incorporated
into newly synthesised DNA. Antibodies that bind specifically to BrdU can then
be used to detect where it is located in a tissue sample. In the adult brain,
the only cells containing new DNA are those that have just been produced by the
division of neural stem cells.
The pairs of young mice had about the same number of newborn neurons in the
dentate gyrus as unpaired mice of the same age. This was also the case for pairs
of old mice. Remarkably, though, the brains of old mice paired with young mice
contained significantly more new cells than unpaired old mice, and those of
young mice paired with old ones contained significantly less than unpaired young
animals.
These results suggest that chemicals found in the blood of old mice inhibit
the generation of new brain cells, whereas chemicals in the blood of young mice
promote it. The researchers then injected blood from young or old mice into
young adults. Again, they found that animals injected with old blood had far
fewer newborn neurons in the hippocampus than those injected with young blood,
confirming that old blood contains soluble factors that inhibit neurogenesis.
Next, they investigated the effects of old blood on cell function. They took
slices of hippocampal tissue from the brains of young mice paired with young and
old ones, and impaled cells with microelectrodes to examine their electrical
properties. In the tissue slices from young mice, a decrease in long-term
potentiation (LTP) was observed. LTP is a form of synaptic plasticity, in which
connections between neurons are strengthened.
As LTP is widely believed to be critical for learning and memory,
Wyss-Coray's group speculated that age-related changes in the composition of
blood may be linked to the decline in cognitive function that occurs with
ageing. To find out, they trained young mice on two different tasks. In the fear
conditioning task, the animals are given a small electric shock at the same time
as a sound is played. When this is done repeatedly, they learn to associate the
two stimuli, and then exhibit fear behaviour (freezing) when they hear the sound
on its own. In the memory task, the animals are placed into a water maze, and
quickly learn the location of a hidden platform.
All of the mice performed similarly on both tasks. After the training, some
of them were injected with blood from old mice, and made to perform the same
tasks again. The performance of these animals on both tasks worsened – they
exhibited less freezing when played the sound in the fear conditioning task, and
an impaired ability to remember the location of the submerged platform in the
water maze.
Finally, the researchers used a technique called proteomics to compare the
proteins found in blood from young and old mice before and after pairing them
with animals of the same or a different age. They identified six signalling
molecules whose levels were elevated in both young animals paired with old ones
and unpaired old mice.
One of these, CCL11, decreased neurogenesis when injected into the
bloodstream of young mice or directly into the hippocampus, but this effect was
abolished when it was administered with a neutralizing antibody. CCL11 also
impaired their performance on the fear conditioning and memory tasks, and
inhibited the differentiation of neural stem cells maintained in a culture
dish.
Together, these results show that age-related changes in the composition of
blood are linked to the decline in adult neurogenesis that occurs with age.
The
researchers plan to use a similar approach to identify the proteins in young
blood that stimulate neurogenesis.
They also suggest that these rejuvenating
factors have the potential to alleviate the decline in cognitive function that
occurs with ageing.
Reference: Villeda, S et al
(2011). The ageing systemic milieu negatively regulates neurogenesis and
cognitive function. Nature, DOI: 10.1038/nature10357
http://www.guardian.co.uk/science/neurophilosophy/2011/sep/05/young-blood-rejuvenates-old-brains
|
|
Joined: 12/12/2011
Posts: 5159
|
I think the pathway is this: eotaxin stimulates a g protein-coupled receptor--activates phospholipase C beta--activates protein kinase C-- causes the formation of peroxynitrites--oxidizes adrenergic receptors-- inhibits neurogenesis. High levels of eotaxin in the bloodstream increase the risk for Alzheimer's disease.
The argument for Gammagard (intravenous immunoglobulin) is that it treats Alzheimer's disease by lowering plaque levels, but this article (I just skipped to the conclusion because the rest of the article was too complicated for me) suggests another mechanism.
Conclusions
We found no in vivo support of Aβ clearance from the brains of hIVIG treated transgenic mice either due to disintegration or phagocytosis.
Treatment with hIVIG suppressed TNF-α gene expression and fostered neurogenesis in the dentate gyrus.
http://www.jneuroinflammation.com/content/9/1/105
Protein kinase C increases TNF-a gene expression which leads to the formation of peroxynitrites (and peroxynitrites increase Protein kinase C activity).
The data indicate that TNF-induced PKC activation mediates ONOO- generation, which results in the oxidation and depletion of glutathione...
http://www.ncbi.nlm.nih.gov/pubmed/7485529
Peroxynitrites oxidize adrenergic receptors which inhibits neurogenesis. Exercise increases the activation of these receptors and increases neurogenesis.
I love the highlighted quote from Richard Ransohoff: stems cells in the hippocampus do not die during Alzheimer's disease. The problem is the receptors needed to stimulate their regrowth of neurons (neurogenesis) is blocked (due to oxidation). Unlike the unfounded argument that past a certain point Alzheimer's disease cannot be treated because too many neurons have died; the fact of the matter is that if the oxidation of certain receptors are reversed neurons in the hippocampus can be regenerated, so that at least partially Alzheimer's disease can be reversed at any stage.
|
|
Joined: 12/12/2011
Posts: 5159
|
It may be as simple as this, immunoglobulin in the new blood lowers eotaxin levels which inhibits the formation of peroxynitrites, maintains glutathione levels (the body's master antioxidant), and thus inhibits and partially reverses the oxidation of adrenergic receptors, thus allowing for the formation of new neurons.
(Immunoglobulin G4,anti-(human eotaxin 1) (human monoclonal CAT-213 g4-chain), disulfide with human monoclonal CAT-213 k-chain, dimer )
I always take case studies seriously. When significant improvement is observed there is almost always a reason behind it.
Thanks, Onward for always making me think even when I don't always think clearly. Never in a million years would I have thought about this.
|
|
Joined: 12/20/2011
Posts: 217
|
Lane, thanks yet again for your input.
(As usual, the science is way over my head.)
|
|
Joined: 12/12/2011
Posts: 5159
|
Not sure if these charts will help at all, but sometimes it is easier to see the pathways than to try to describe them.
The pathway to the right (looking at the picture) is the one that leads to Alzheimer's disease. Eoxtaxin levels increase with age and could play a role in some cases in Alzheimer's disease. Gammagard (intravenous immunoglobulin) helps to remove eotaxin.
The next diagram is a blow up of sorts of the right side of the above diagram.
NADPH oxidase (found in the first diagram) leads to the production of superoxide anion and NFkB (found in the second diagram) leads to the production of inducible nitric oxide. The two combine to form peroxynitrites.
The last diagram shows all the pathways that lead to (phospholipase C gamma and beta) Alzheimer's disease or protect against it (phosphatidylinositol 3 kinase/Akt).
Various phenolic compounds (berries and other fruits, spices, essential oils, herbs, cocoa, teas, etc.) inhibit the activation phospholipase C gamma and polyunsaturated fats (such as fish oil) inhibit the activity of both phospholipase C gamma and beta. This is the route to at least delay the onset of Alzheimer's disease.
http://www.ncbi.nlm.nih.gov/pubmed/16266772
The best way to treat the disease even very late is with methoxyphenols such as eugenol in various essential oils via aromatherapy.
|
|
Joined: 12/12/2011
Posts: 5159
|
One more diagram. Factors that increase myo-inositol levels and thus the risk for Alzheimer's disease are high glucose levels (diabetic or pre-diabetic), high blood pressure due to high levels of sodium, and Down syndrome (because individuals with Down syndrome have an extra chromosome for the sodium/myo-inositol transporter). When one considers how many factors can contribute to this disease through this pathway from diet, lifestyle, genetics, environmental toxins, drugs, stress, chronic bacterial and viral infections, and even changes in blood composition no wonder Alzheimer's disease is so prevalent.
|
|
Joined: 12/12/2011
Posts: 5159
|
Using the above diagrams, this is a description of what leads to amyloid plaques.
Various first messengers linked to phospholipase C, including acetylcholine and interleukin 1, regulate the production both of the secreted form of the amyloid protein precursor (APP) and of amyloid beta-protein. We have now identified intracellular signals which are responsible for mediating these effects. We show that activation of phospholipase C may affect APP processing by either of two pathways, one involving an increase in protein kinase C and the other an increase in cytoplasmic calcium levels. The effects of calcium on APP processing appear to be independent of protein kinase C activation. The observed effects of calcium on APP processing may be of therapeutic utility.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC43811/
Protein kinase C processes the amyloid precursor protein and it is a calcium driven enzyme that cleaves that protein into amyloid plaques. There is some suggestions that Protein kinase C may actually cleave the amyloid precursor protein in a way that inhibit the formation of plaques (until intracellular calcium reaches high levels). Protein kinase C increases formation of peroxynitrites (by increasing superoxide anions via NADPH oxidase and inducible nitric oxide via Nuclear factor kappa B) even before the appearance of plaques. Thus, part of the damage to the brain begins before the formation of amyloid plaques and in some cases that damage may proceed with few if any amyloid plaques. So don't go after the plaques--go after what caused the plaques and more importantly peroxynitrites to form in the first place (phospholipase C gamma and/or beta) and go after the peroxynitrites. And the same compounds do both (phenols, for example), although some more effectively than others.
|
|
Joined: 4/24/2012
Posts: 484
|
This is amazing information. Thank you. I am understanding this phospholipase C - protein kinase C pathway better and the possible effects of peroxynitrites on neurogenesis. This is the first I've heard of Eotaxin (CCL11). It sounds like a great target for AD since its increase can be linked to cognitive decline and it fits with the implication of protein kinase C, etc.
I am trying to make some connections between this information and two other treatments that have been shown to be effective and have a strong theory of the mechanism of action behind them. The first is Rapamycin and the inhibition of mTOR. The second is the RXR agonist Bexarotene.(both currently available off label)
Rapamycin
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0009979
Bexarotene
http://www.sciencemag.org/content/335/6075/1503.abstract
I don't have the background to understand and put all this together but I think these things may all support each other in revealing the mechanisms of AD and a potential treatment that we can access immediately. Rapamycin affects mTOR which is a phosphatidylinositol 3-kinase (mentioned in Lane's previous diagram) and a signaling protein sensitive to insulin, serum, and oxidative stress. What I like about mTOR is that it is also inhibited by caloric restriction or fasting which fits well with the theory that AD is related to diet.
We know that ApoE 4 gene plays a part in AD. Normally this gene activates Apolipoprotien E which protects against AD somehow. How does this fit into the protein kinase C/phospholipase C explanation? My mother is positive for this gene.
Thanks for any suggestions or observations or thoughts you may have on this.
|
|
|
|