I'm late to comment on this, but I have read Grant's post a few times now, and think his idea that retinol is the culprit behind all this mayhem is compelling.
I came across a paper today that brought to mind Grant's post, so I wanted to share some quotes from it here. @hillcountry I think you'll like this one, if you haven't seen it yet.
“It is possible that its [TTR] capacity to bind many classes of compounds allows it to serve as an endogenous detoxifier of molecules with potential pathologic effects.”
So, if TTR is detoxifying “molecules with pathologic effects,” could there be a tipping point where there are too many toxins for the body to remove? And if so, is that when TTR (in an effort to contain the toxins and protect the cells from them, as John describes above) starts gumming up the works?
From the same source (summary):
“At this stage of our knowledge, it is certainly not appropriate to state that we know all there is to know about the biologic functions of TTR. The mechanism of its impact on normal neuronal function is not clear. While it may be independent of its function as a retinol carrier, sufficient data are not yet available to show that this is truly the case. The protein plays a role in pancreatic and retinal epithelial function. Whether it is critical in disease states affecting these organs is currently unknown, the available data being too fragmentary to draw definitive conclusions. What is quite striking is that TTR can be either an amyloid precursor or a defense against tissue amyloid fibrillogenesis depending on the cell of expression. The general mechanism of amyloid formation from either wild-type or mutant TTR precursor appears to be clear. The detailed or even general understanding of its functions in other organs is not yet in hand. Does it “chaperone” Aβ or pancreatic amyloidogenic precursors intra- or extracellularly? If so, what are the structural features that are responsible for those functions? It has often been said that the differences between law breakers and law enforcers is a very fine line; is the same true for amyloid precursors and molecules that are in fact anti-amyloidogenic?”
I'm late to comment on this, but I have read Grant's post a few times now, and think his idea that retinol is the culprit behind all this mayhem is compelling.
I came across a paper today that brought to mind Grant's post, so I wanted to share some quotes from it here.
@hillcountry I think you'll like this one, if you haven't seen it yet.
“It is possible that its [TTR] capacity to bind many classes of compounds allows it to serve as an endogenous detoxifier of molecules with potential pathologic effects.”
So, if TTR is detoxifying “molecules with pathologic effects,” could there be a tipping point where there are too many toxins for the body to remove? And if so, is that when TTR (in an effort to contain the toxins and protect the cells from them, as John describes above) starts gumming up the works?
From the same source (summary):
“At this stage of our knowledge, it is certainly not appropriate to state that we know all there is to know about the biologic functions of TTR. The mechanism of its impact on normal neuronal function is not clear. While it may be independent of its function as a retinol carrier, sufficient data are not yet available to show that this is truly the case. The protein plays a role in pancreatic and retinal epithelial function. Whether it is critical in disease states affecting these organs is currently unknown, the available data being too fragmentary to draw definitive conclusions. What is quite striking is that TTR can be either an amyloid precursor or a defense against tissue amyloid fibrillogenesis depending on the cell of expression. The general mechanism of amyloid formation from either wild-type or mutant TTR precursor appears to be clear. The detailed or even general understanding of its functions in other organs is not yet in hand. Does it “chaperone” Aβ or pancreatic amyloidogenic precursors intra- or extracellularly? If so, what are the structural features that are responsible for those functions? It has often been said that the differences between law breakers and law enforcers is a very fine line; is the same true for amyloid precursors and molecules that are in fact anti-amyloidogenic?”
