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Brain Fact: Neurofibrillary Tangles · Do You F*cking Mind?

• 0:16
  Speaker 1: Let's get straight into it.
• 0:17
  Speaker 2: So the brain fact of today, neurofibullary tangles. We're going
• 0:22
  Speaker 2: to talk about this molecular mechanism that goes on behind
• 0:25
  Speaker 2: these tangles. Now, and before I go into it, I mean,
• 0:28
  Speaker 2: I always get great feedback. Everyone fucking loves the brain facts.
• 0:31
  Speaker 2: That's like one of the main dams I get is
• 0:33
  Speaker 2: brain facts. But it's a bit like tedious and science y,
• 0:36
  Speaker 2: and I understand that some people are here just to
• 0:38
  Speaker 2: listen to more of like the psychology side of things.
• 0:41
  Speaker 2: So if that is you maybe fast forward it too
• 0:43
  Speaker 2: roughly like the ten minute or eleven minute mark ish,
• 0:47
  Speaker 2: if you're not into like hacktic science and like sell
• 0:50
  Speaker 2: anatomy and shit like that. I fucking live and breathe
• 0:53
  Speaker 2: it and thrive on it. But yeah, little disclaimer now,
• 0:57
  Speaker 2: like I mentioned before, when it comes to amyloid plaques
• 1:01
  Speaker 2: in the brain for Alzheimer's.
• 1:03
  Speaker 1: Disease, it's a hypothesis.
• 1:05
  Speaker 2: Okay, there's a very heavy theory that this is the
• 1:10
  Speaker 2: cause of Alzheimer's disease. But what we're not sure about
• 1:13
  Speaker 2: is is it just heavily involved or is it the cause. Now,
• 1:17
  Speaker 2: another hypothesis which happens alongside these amyloid plaques is the
• 1:23
  Speaker 2: neurofibillary tangles and it's called the Tao hypothesis.
• 1:28
  Speaker 1: Okay, this one about the neurofibrillary tangles.
• 1:31
  Speaker 2: If you have studied Alzheimer's disease, anything around neuroscience and
• 1:35
  Speaker 2: I of that, you've definitely heard of the Tau hypothesis.
• 1:37
  Speaker 1: Okay, so let's go into it.
• 1:40
  Speaker 2: Neurofibrillary tangles. It's kind of like these plaques that I
• 1:44
  Speaker 2: was talking about in the sense that it's things that
• 1:45
  Speaker 2: clump together.
• 1:46
  Speaker 1: These are slightly it's made up of.
• 1:48
  Speaker 2: Something different, but it's these clumps of tangles, and they
• 1:51
  Speaker 2: happen due to the misfolding of a protein called tao.
• 1:55
  Speaker 1: Okay, and this happens to a different reason to amyloid plarks.
• 2:00
  Speaker 2: What we're dealing with here is something called a prion
• 2:03
  Speaker 2: where you have a protein and proteins are kind of
• 2:07
  Speaker 2: coiled up and packaged in a very specific conformation, like
• 2:10
  Speaker 2: very specific way, right, And if it's not folded properly,
• 2:17
  Speaker 2: it's a misfolded protein and that is called a prion.
• 2:20
  Speaker 2: And the prion is what then goes on to cause
• 2:24
  Speaker 2: damage through a whole series of events, right, it's that prion.
• 2:28
  Speaker 2: It's the misfolded protein. For whatever reason, something's gone on
• 2:31
  Speaker 2: in the folding of the protein. And then fucking how
• 2:34
  Speaker 2: you going, We've got issues.
• 2:36
  Speaker 1: Now.
• 2:37
  Speaker 2: The TAE hypothesis is saying that Alzheimer's disease is caused
• 2:41
  Speaker 2: by the misfolding of the TAW protein. So what is
• 2:44
  Speaker 2: the role of TAW Normally, so within the cytoskeleton of
• 2:50
  Speaker 2: the neuron. So that's the structure of the neuron. So
• 2:53
  Speaker 2: imagine that neurons have their own little version of the skeleton. Right,
• 2:57
  Speaker 2: So you've got like the so much, which is like
• 2:59
  Speaker 2: the body of the cell. You've got all these extensions
• 3:01
  Speaker 2: that reach out. You've got the axon and the dendrites
• 3:04
  Speaker 2: and all these bits that reach out to be able
• 3:05
  Speaker 2: to connect to other cells. I'm kind of like you
• 3:07
  Speaker 2: should see my hand movements trying to explain it to you,
• 3:10
  Speaker 2: even though you could just hear my voice. Now, that
• 3:13
  Speaker 2: neuron has a kind of skeleton, and it's called a cytoskeleton,
• 3:17
  Speaker 2: and it's inside the neuron obviously, and it helps maintain
• 3:21
  Speaker 2: the structure of the cell, but it also helps transport
• 3:24
  Speaker 2: this cytoskeleton skeletal structure within the cells, helps transport nutrients
• 3:28
  Speaker 2: across that cell to keep it, you know, to keep
• 3:32
  Speaker 2: it running smoothly. And we've got something called microtubules within
• 3:36
  Speaker 2: this cytoskeleton, microtubules, and these form part of the structure
• 3:40
  Speaker 2: and the integrity of the neuron. Like I said, it's
• 3:42
  Speaker 2: the microtubules that help transport nutrients across the cell, helps
• 3:46
  Speaker 2: maintain its shape and its structure. And these microtubules have
• 3:50
  Speaker 2: the ability to stretch out longer or to get shorter,
• 3:54
  Speaker 2: and when it shortens, it can fall apart. And this
• 3:58
  Speaker 2: is known as the actual term for it is a
• 4:01
  Speaker 2: microtubule catastrophe.
• 4:03
  Speaker 1: Loll love how dramatic that is.
• 4:05
  Speaker 2: And it is the role of Tao, this Tau protein
• 4:09
  Speaker 2: to prevent it from falling apart when it gets shortened.
• 4:12
  Speaker 2: So it allows for this lengthening and shortening, but it
• 4:15
  Speaker 2: prevents this microtubule catastrophe from happening. So if Tau was
• 4:20
  Speaker 2: not present another thing that Tao does. If Tao was
• 4:23
  Speaker 2: not there, these microtubules would not hold together, so they
• 4:27
  Speaker 2: would just float off and they wouldn't have this specific
• 4:30
  Speaker 2: structure where there's where all the parts that make up
• 4:33
  Speaker 2: the microtubule that when you look at diagrams off it. It
• 4:35
  Speaker 2: looks like all these little beads or bubbles that are
• 4:37
  Speaker 2: stuck together, and it's the Tau protein that keeps that
• 4:41
  Speaker 2: tube of bubbles stuck together. If the towel wasn't there,
• 4:44
  Speaker 2: wouldn't hold together. Now there's a protein called Tao protein
• 4:48
  Speaker 2: kinase one. It's just another protein and it phosphorylates tao.
• 4:54
  Speaker 2: When you hear something, when I talk about phosphorylation or phosphorulates,
• 4:57
  Speaker 2: it's basically adding a phosphate group.
• 5:00
  Speaker 1: To something else. Okay, something is getting phosphate group added
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  Speaker 1: to it and.
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  Speaker 2: It's turning it into So this phosphorylation occurs, and then
• 5:09
  Speaker 2: Tau protein kinase turns Tao into something called tau.
• 5:13
  Speaker 1: Phosphate because it has a phosphate group added to it.
• 5:16
  Speaker 2: When Tao is in its phosphorylated state, it's teu phosphate.
• 5:21
  Speaker 2: How many times do I want to say taophosphate. It
• 5:23
  Speaker 2: has the ability to stabilize these microtubules. The issue in
• 5:29
  Speaker 2: this whole Tau hypothesis is when it gets hyperphosphorylated. That's
• 5:34
  Speaker 2: when there's too much phosphorylation going on. So it's not
• 5:37
  Speaker 2: going to do its job and it can't stabilize the
• 5:39
  Speaker 2: microtribules because just too.
• 5:41
  Speaker 1: Much of it has gone down.
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  Speaker 2: And in Alzheimer's disease, for some reason, these tau proteins
• 5:45
  Speaker 2: are hyper phosphorylated, which means that it's just happening too much,
• 5:50
  Speaker 2: so that whole process leads to the failure of the microtubules.
• 5:54
  Speaker 2: And what causes this, So what they're thing thinking what
• 6:00
  Speaker 2: it's believed based.
• 6:02
  Speaker 1: On what we've found, what scientists have found.
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  Speaker 2: It's believed that inflammation of some sort activates that tau
• 6:09
  Speaker 2: protein kinase, the one that adds the phosphate group, but
• 6:14
  Speaker 2: more so than normal. So instead of just activating it
• 6:17
  Speaker 2: to do its job, it hyperactivates it, which then causes hyperphosphorylation.
• 6:22
  Speaker 2: And because of this, the microtribules start to break apart
• 6:25
  Speaker 2: or collapse, and it has lost or it starts to
• 6:28
  Speaker 2: lose its integrity and its structure. Then bits of tau protein,
• 6:32
  Speaker 2: which are now hyperphosphorylated, detach from those microtubules.
• 6:37
  Speaker 1: They just float off, and.
• 6:39
  Speaker 2: Then they clump together. And these clumps of detached tau
• 6:42
  Speaker 2: proteins which are hyperfosphorylated, are called neurofibrillary tangles. Now the
• 6:47
  Speaker 2: microtubules that are left can't actually do their normal function.
• 6:51
  Speaker 2: They can't transport nutrients, and they can't do cell trafficking,
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  Speaker 2: which is needed for the cells to function. And these
• 6:58
  Speaker 2: tangles that are formed to get spread throughout the cell,
• 7:01
  Speaker 2: in the inside of the cell. So with amyloid pluques,
• 7:04
  Speaker 2: it's outside the cell structure. With tao, it happens in
• 7:08
  Speaker 2: and outside, but definitely inside the cell structure. And these
• 7:12
  Speaker 2: they form these large aggregates called neurofibrillary tangles, and they
• 7:17
  Speaker 2: also induce cell death. Okay, they can also spread, like
• 7:22
  Speaker 2: I said, outside of the cell, and when they're outside
• 7:25
  Speaker 2: the cell, they induce inflammation because of the effect that
• 7:28
  Speaker 2: they have on glile cells on the brain.
• 7:30
  Speaker 1: So we know that glile cells.
• 7:32
  Speaker 2: Are like the supporting structure structural cells to the neurons.
• 7:35
  Speaker 2: So for every neuron you've got eighty to one hundred
• 7:38
  Speaker 2: billion neurons in your brain. For every neuron, you've got
• 7:41
  Speaker 2: about ten glile cells. So there's a fucking lot of them, right,
• 7:45
  Speaker 2: And when there's inflammation outside of the cell, you activate
• 7:49
  Speaker 2: certain glile cells which then release these pro inflammatory mediators,
• 7:54
  Speaker 2: which then lead to more inflammation, which then leads to
• 7:57
  Speaker 2: the activation this more inflammation will lead to the avation
• 8:00
  Speaker 2: of tau protein CANSE one, and then that leads to hyperfosphorylation,
• 8:04
  Speaker 2: and then the.
• 8:05
  Speaker 1: Vicious cycle continues.
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  Speaker 2: So that in a nutshell, is neurofibrillary tangles and how
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  Speaker 2: they detached and why.
• 8:11
  Speaker 1: But it's important to note.
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  Speaker 2: That that's not the only inflammation that's going to set
• 8:15
  Speaker 2: off this activation of tau protein kinase one which leads
• 8:18
  Speaker 2: to this phosphorylation. There's all kinds of inflammation, not just
• 8:22
  Speaker 2: the one I mentioned. All kinds of inflammation can cause
• 8:25
  Speaker 2: this whole cascading effect. Yeah, good times. Thought that was
• 8:30
  Speaker 2: interesting if you study the brain. Hopefully that gave you
• 8:33
  Speaker 2: a
• 8:35
  Speaker 1: I don't know, good explanation of that if you're interested.