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0:00
Today, I'm going to
talk to you about
Leucine-rich repeat
kinase 2 or LRRK2.
My name is Mark Cookson.
I'm the Chief of the
Laboratory of Neurogenetics at
the National Institute on Aging.
0:13
First, let me tell you a little
bit about Parkinson's disease,
what it is, and how it
expresses itself in humans.
Parkinson's disease
is a motor disorder.
It's characterized by tremors,
bradykinesia, or
slowness of movement,
rigidity, posture, and gait.
However, Parkinson's disease is
also a multisystem disorder,
so you can have
prodromal symptoms
that occur before
the onset of motor
Parkinson's disease
including things
like REM sleep
behavioral disorder.
Often, later on in
the disease course,
Parkinson's disease
can develop into
a dementing illness
characterized
by cortical dysfunction.
The pathology of Parkinson's
disease is really two parts.
First of all, the cell loss,
and very prominently
dopamine neurons in
the substantial
nigra pars compacta
that project to the
striatum are lost.
But the pathology is also
protein accumulation
pathology and
we have Lewy bodies that
are present across
different brain regions.
1:06
Illustrated here by the
work of Heiko Braak et al.,
you can see that the Lewy
body pathology starts in
very deep brain stem areas
and then progresses up
through the midbrain and then
eventually, into the
cerebral cortex.
1:21
Parkinson's disease pathology is
also a multicellular process.
For example, I said
earlier that neurons and
substantia nigra the
dopamine neurons that
project the striatum are
lost in the disease.
But this is also associated with
the activation of cells
around those dying neurons,
including astrocytes
and microglia.
If we think of
Parkinson's in this way,
it's a multi-system,
multi-pathology, and
multicellular disorder.
