- [Voiceover] So, in most people, right
when we're talking about their Parkinson's Disease
we say that their Parkinson's Disease is Idiopathic.
And that just means that we don't know what caused it.
And that's actually the case for the vast majority of people
with Parkinson's Disease.
About 85% of people.
So that's a lot, right?
But in a handful of people with Parkinson's Disease
about 15%,
we actually do know what caused the disease.
And for these people something's actually gone wrong
with at least one of their genes.
So a quick recap on genes.
Remember that genes are essentially specific
segments of our DNA, right?
So you'd find them in almost every cell in your body.
So, there are specific segments of DNA that provide
instructions to the cell.
And each gene is like a special recipe.
So each gene has instructions for
how to make different proteins.
And once these proteins are made
they go off and they do tons of different tasks.
Tons of different important tasks all around our bodies.
Like, well, basically everything.
Basically everything is done by proteins.
>From creating our cellular structure
to our organs, to our enzymes.
Those are proteins too.
Essentially every structure or process in our bodies
that you can even think of,
absolutely everything,
somehow involves proteins.
So when something goes wrong with our genes,
let's say its supposed to look like this, right?
but maybe due to a mutation,
a change in that gene,
it ends up actually looking kinda different.
So maybe something like this here.
Now all of a sudden the instructions,
the recipe that that gene has for making their proteins,
they're not correct anymore, right, they're not the same.
And so the proteins that should be made,
the proteins that we want these genes to make,
now they can't be made properly anymore.
At least in cells that have these genes that are affected,
that are changed, that are mutated.
And when proteins aren't made properly
well, they won't be able to carry out their normal
roles anymore, right?
So we actually have a collection of genes,
a family of genes, that when they're changed,
when they're mutated in some way
can either directly cause or increase our chance
of developing Parkinson's Disease
and this depends on which gene gets mutated.
Now remember how we get our DNA,
how we get our chromosomes.
So we have 23 single chromosomes that we
get from our dad and we get another 23 single
chromosomes from our mom.
And they form pairs so we end up with
23 pairs of chromosomes, right?
So that means that we have two copies of each gene.
Right?
One copy came from your mom
and one copy came from your dad.
Now let's actually classify genetic causes
of Parkinson's Disease into two groups.
So two types of inheritance if you will.
So we'll say Autosomal Dominant over here.
And we'll say Autosomal Recessive over here on this side.
And this'll all start to make sense in a minute here.
And the inheritance patterns can get really
detailed and messy.
So I'm not gonna really go into all that at the moment.
But basically I wanna get across here that the
Autosomal Dominant types of Parkinson's Disease
or really any other disease that's inherited
in an Autosomal Dominant way,
you only really need one bad copy of the gene.
So either one bad copy from your mom,
or one bad copy from your dad.
And that would be enough to cause the disease.
So in this case, in our case that's Parkinson's Disease.
And Autosomal Recessive,
well that means that both mom and dad need to
pass on to you a mutated copy of the gene.
And there's one other thing I should mention.
So when we say that a gene mutation causes a disease.
So in this case we say a gene mutation causes
Parkinson's Disease,
we can either mean that it definitely causes the disease,
100%.
So if you get the mutated copy or if it needs two copies
of the gene you will definitely develop the disease.
Or, we can mean that getting the mutated copy,
or copies, will increase your chance
of developing the disease.
So those two things are a little different, right?
And for some genes, certain mutations within that gene
will definitely cause the disease and other mutations in
that gene may just increase the chance
of the disease developing.
And that's because different mutations in a gene
effect the genes protein in different ways, right?
So some mutations may be more detrimental than others.
So that can increase the chance of the disease developing.
So as we're chatting about these mutated genes
that we're gonna get to that are relevant
to Parkinson's Disease,
we're just gonna say that they can cause the disease.
But in the back of our minds we just have to remember
that depending on which mutation in the gene is happening,
because there can be quite a few different ones in one gene,
and this is still being researched, right?
The mutation can either 100% cause the disease
or just increase the chances of developing a disease.
Okay.
So there are five main genes that we know about.
So there are a few more but there's five main ones
that when they're mutated in some way can
cause Parkinson's Disease.
So we won't go into all of these genes
but let's go over a few of the genes
that are a bit more commonly mutated.
So let's head over here to our first chromosome.
Chromosome #1.
So here's our first chromosome so it's just--
it's just hanging out here.
And right about here we have a gene called Park7,
and Park7 it has instructions for making a protein
called DJ-1.
So here's DJ-1 here.
And DJ-1 kinda makes me think of a mom,
when I think about what DJ-1 does I think of--
I think of a mom.
It does things like protecting and guiding.
Right?
Protecting and guiding our molecules around our body.
You know, like how your mom protects and guides you, right?
So, it helps protect our cells,
it helps protect them during situations
that stress our cells out.
And it helps guide our proteins.
So it helps guide them to do things like
make sure they're folding in the correct
three-dimensional shape.
Because remember our proteins--
our proteins need to get into a certain shape
in order to be able to function properly, right?
And DJ-1 also helps to make sure that damaged proteins,
proteins that we don't want anymore,
are sent off to be broken down.
Because otherwise they kinda pile up in our cells
and they get in the way, right?
Now, this last ones not very mom-like.
I'm sure none of our moms would send us off to be degraded.
But anyway...
So those are some of the main tasks of DJ-1.
So some mutations in the gene Park7
can cause Parkinson's Disease and Park7
is one of those genes where you need to get a mutated
copy from both your mom and your dad
in order to develop Parkinson's Disease.
So this would be considered an Autosomal Recessive
cause of Parkinson's Disease and it's actually
responsible for early-onset Parkinson's Disease.
So Parkinson's that's diagnosed before the age of
50 years old.
So when Park7 is mutated,
when the gene's DNA is changed in some way,
that changes the instructions
on how to make the DJ-1 protein, right?
Because the gene carries a recipe for that protein.
So when this is changed DJ-1 isn't made properly
and therefore it can't function properly.
It can't do all of these important mom-like tasks
that we talked about.
So that's Park7 and DJ-1.
So, what's our next gene?
Let's jump over here to Chromosome 6
and let's check out our next gene.
So about here on Chromosome 6, about here,
this is where our Park2 gene is.
And for a mutation in this gene to cause Parkinson's Disease
it would need to be inherited in an
Autosomal Recessive way as well.
A mutated copy from both your mom and your dad.
Oh, and something that's really interesting is that the
Park2 gene is one of the largest genes that we humans
have in our whole body.
So it's one of the biggest genes that we have.
So Park2, it encodes for a protein called Parkin.
So let's draw, let's draw a little Parkin protein here.
And Parkin has this really, really important role.
What it does is it tags other proteins that are damaged
or that we have too many of,
they're in excess.
And it tags them with this molecule called Ubiquitin.
So Ubiquitin is like a, it's like a little flag,
it's a flag that alerts our cells to shuttle these proteins
that we don't want--
that we don't want anymore.
And it alerts them to shuttle them to these structures
in our cells called Proteasomes.
And this is where those proteins that we don't want
get broken down and disposed of.
So Proteasomes are kinda like the waste disposal
facility in our cells.
So Parkin is really, really important for making sure
that we don't have all these excess or damaged proteins
kinda piling up in our cells and getting in the way.
So we actually know of a couple hundred different
Park2 mutations that can cause Parkinson's Disease.
So, some of the mutations are associated with the
juvenile form of Parkinson's Disease
which is essentially an extremely early-onset type of
Parkinson's Disease relatively speaking to when it
normally comes on.
So, when people are diagnosed before the age of 20.
And some other Park2 mutations,
they're associaated with late-onset Parkinson's Disease,
which is when people are diagnosed after
the age of 50 years old.
But in either case,
whether it's early or late Parkinson's Disease,
these mutations have changed the gene a bit, right?
They've changed our instructions for making Parkin.
And so we end up with a non-functional Parkin protein,
a Parkin protein that just can't do what it needs to do.
It can't function properly,
it can't tag these damaged proteins
so that we get rid of them.
So our last gene that we're gonna look at
is over here on Chromosome 12.
So here's Chromosome 12 here,
I'll just draw it out.
And the gene that we're interested in is the LRRK2 gene.
So I'm gonna call it Lark2,
it's just a little easier to say.
And it sits about here.
So Lark2 gives us the recipe
to make the protein Dardarin.
And Dardain helps us do things like
turn our cells on and off so that we can control their
activity and send signals around the brain so that
different cells can talk to each other.
And what's really interesting is Lark2 mutations
are actually the most common gene mutation
that is associated with Parkinson's Disease.
So this is the gene that we normally see issues with
in people that have a genetic form of the disease.
And with this particular gene people need to only get
one mutated copy from either of their parents
rather than both.
So this an Autosomal Dominant genetic cause of
Parkinson's Disease and just like before when
our Lark2 gene gets mutated we end up with a malformed
a damaged Dardarin protein being formed, right?
So it's being produced by transcription and translation,
but since we've damaged the Lark2 gene in some way
the instructions are all wrong.
So the protein ends up being formed a little differently
so it can't function properly in order to carry out
its really important roles.
So we've gone through some of these gene mutations
that can cause Parkinson's Disease but by now you must be
wondering, "Yeah, I get that, I get that Park7 and Park2
and the Lark2 can get mutated and produce malformed
proteins and then they can't do their jobs correctly,
etcetera, etcetera, but what does that have to do with
Parkinson's Disease?
How does that cause Parkinson's Disease?"
And that's an excellent question.
And the answer as it stands right now
is that we actually don't know.
We don't know how these genes getting mutated
and these proteins being malformed,
we don't know how that actually leads to the disease.
We just know that we consistently see
Parkinson's Disease development
in people with these gene mutations
but we don't yet know,
kinda step-by-step
how people with these mutations
actually develop Parkinson's Disease.
So, for now, we'll just have to stay tuned
into the ongoing research efforts
to find out more about this one.