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    I would like to know why amyloid plaques (deposits in the brain of a sticky protein called amyloid beta peptide) "causes" neurodegeneration? I am aware that it doesn't directly CAUSE neurodegenerenation, but I want to know why that protein is so special in Alzheimer's Disease. Do neurons die because of it?
    If I were to say that Alzheimer's Disease is a Tauopathy, I would be saying that it is "caused" by neurofibrilary tangles (overexpression of tau protein), right? So this amyloid plaque would not be that relevant?
    Research done in this area, in tauopathies, has the aim of trying to find out a drug, compound, that will have a positive effect on reducing the amount of tau protein produced in the brain. Would this be a possible cure for Alzheimer's Disease and other tauopathies? Why do we want to reduce the amount of tau protein produced in the brain? To see if it is the cause of neurodegenerative diseases?
    Please help. Do answer. Even if you do not have any good knowledge on this matter, I would like to know what you think and what makes sense to you. It can get me started. Thanks for at least reading
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    Oi! I just made two ginormous postings on this and now they've disappeared. Well, luckily for you (the general public), I saved it elsewhere :p:

    Repost:

    (Original post by mindmystery)
    I would like to know why amyloid plaques (deposits in the brain of a sticky protein called amyloid beta peptide) "causes" neurodegeneration? I am aware that it doesn't directly CAUSE neurodegenerenation, but I want to know why that protein is so special in Alzheimer's Disease. Do neurons die because of it?
    If I were to say that Alzheimer's Disease is a Tauopathy, I would be saying that it is "caused" by neurofibrilary tangles (overexpression of tau protein), right? So this amyloid plaque would not be that relevant?
    Research done in this area, in tauopathies, has the aim of trying to find out a drug, compound, that will have a positive effect on reducing the amount of tau protein produced in the brain. Would this be a possible cure for Alzheimer's Disease and other tauopathies? Why do we want to reduce the amount of tau protein produced in the brain? To see if it is the cause of neurodegenerative diseases?
    Please help. Do answer. Even if you do not have any good knowledge on this matter, I would like to know what you think and what makes sense to you. It can get me started. Thanks for at least reading
    Hi, first of all, I want to say I'm no expert whatsoever, and am answering from a state of curious ignorance.

    What I can find on amyloid plaques causing neuron death is:

    The key event leading to AD appears to be the formation of a peptide (protein) known as amyloid beta (beta amyloid, Aß) which clusters into amyloid plaques (senile plaques) on the blood vessels and on the outside surface of neurons of the brain -- which ultimately leads to the killing of neurons. A first sketch of the amyloid cascade of events in AD would therefore be:
    Aß formation => amyloid plaques => neuron death => dementia
    (from http://www.benbest.com/lifeext/Alzheimer.html)

    Following amyloid plaque formation two processes play an important role in causing the death of neurons: (1) inflammation and (2) NeuroFibrillary Tangles (NFTs).
    One of the types of cell that reactes to inflammation (and I think inflammation is caused by the plaques' presense, but it's not that clear) causes free radical production, which it seems helps kill neurons.

    I think most people seem to think that both amyloid plaques and tau proteins misbehaving have a part in alzheimers (I just read something referring to a "religious" war between the "tauists" and the "ßaptists" [])

    One interesting thing: sticking amyloid plaque into neurons grown in culture/primates lead to NeuroFibrillary Tangles (NFTs),made up of over-phosphorylated tau protein binding to each other, rather than stabilizing microtubules (poss. because the amyloid beta makes it easier for calcium ions to get into neurons (maybe by forming pores, apparently?), which then causes calcium-activated kinases to do the excessive phosphorylating of the tau proteins.

    So it could be that the NFT comes from the amyloid plaques (which come from a problem with the genes).

    Another interesting thing:
    Amyloid beta is always a feature of AD [Alzheimers Disease], but NFTs are not.
    and
    Amyloid plaque is insufficient to cause the cell death of AD whereas the presence of tau is always associated with AD neurodegeneration. Tau knock-out mice (ie, transgenic mice with no gene for tau) are resistant to Aß-induced toxicity.
    The reasons I can find for NFT equalling cell death are:

    *tau protein normally stabilizes microtubules. Without this stabilization (when the tau's are otherwise engaged with each other), the microtubules are ka-put and the cells are screwed.
    *NFTs bind to proteasomes, reducing their ability to remove dodgey (or just no longer needed) proteins from the cell. So that's not healthy.

    Another poss. causer of AD:
    Neurons are normally non-dividing (post-mitotic) cells, but neurons that have entered an aberrant cell cycle are frequently found in Alzheimer's Disease (AD). Aberrant cell cycle induction may be the primary cause of neuron death in AD, and precede Aß as well as NFT formation.
    . It doesn't say what causes the abnormal cell cycle, but it's interesting if that's separate from NFT and beta amyloid.

    Why have I spent so much time on this? 1. It's interesting 2. I'm avoiding writing up some stuff about yeast protein-degradation pathways. You know, due about 2 weeks ago...

    What are you starting on? Where'd your interest in this come from? Let me know what you think on this - I'm an utter learner, but curious.
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    (Original post by mindmystery)
    Research done in this area, in tauopathies, has the aim of trying to find out a drug, compound, that will have a positive effect on reducing the amount of tau protein produced in the brain. Would this be a possible cure for Alzheimer's Disease and other tauopathies? Why do we want to reduce the amount of tau protein produced in the brain? To see if it is the cause of neurodegenerative diseases?
    From the result I put in the previous post about the mice with the tau gene knocked out being resistant beta amylase induced toxity would suggest that it'd be good to get rid of tau production.

    However, from what I can see logically from the rest of what I read, you'd think that stopping tau production would be bad 'cause then your microtubules (damn important in intra-cellular transport of organelles, chromosomes etc) would have no tau to stabilize them, and so all your cells would die. But then there's the idea that the NFT made from hyper-phosphorlyated tau does bad things to the cell.

    But maybe you could get to a mid-point of tau-levels to reduce both these effects?

    ...This is all just speculation on my part.
 
 
 
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