The title of my talk is
Expanding Roles of RNA-Binding Proteins in Neurodegenerative Diseases.
My name is Aaron Gitler;
I'm a professor in the Department of Genetics at Stanford University School of Medicine.
My laboratory is interested in the mechanisms of human neurodegenerative diseases.
These diseases include Alzheimer's disease,
Parkinson's disease, Huntington's and ALS.
As our population continues to age,
these diseases are increasing in prevalence.
They have several different clinical presentations, ranging from
memory loss in Alzheimer's disease to movement impairments in Parkinson's disease.
Despite these differences in clinical presentation,
there's a common theme that unites
all neurodegenerative diseases - and this is protein misfolding.
Proteins accumulate and aggregate in the brains of patients affected with these diseases,
and my laboratory is trying to understand the cellular pathways affected,
when misfolded human disease proteins aggregate.
Today, I'm going to be talking about
one neurodegenerative disease called Amyotrophic Lateral Sclerosis,
and using it as an example of
how we study protein misfolding and how
RNA-binding proteins play an important role in this disease.
Amyotrophic Lateral Sclerosis, also known as ALS,
in the United States known as Lou Gehrig disease,
after the famous New York Yankees first baseman,
and in Europe as Motor Neurone disease.
This is a disease that affects adults in mid-to-late life,
and is associated with progressive muscle weakness and
eventually muscle loss caused by
a selective loss of motor neurons in the brain-stem and spinal cord.
Loss of these motor neurons leads to muscle weakness,
paralysis and then ultimately death,
typically two to five years after onset.
ALS, like other neurodegenerative diseases comes in a sporadic form or a familial form.
About 90% of ALS cases are sporadic and 10% are familial.
Even though the familial forms are rarer,
they've played important roles in helping us to understand the causes of ALS,
because specific genes can be identified that when mutated cause familial ALS,
and defining those genes can provide insight into cellular pathways that are affected.
The first gene identified that causes ALS when mutated
is SOD1 which encodes the enzyme superoxide dismutase 1.
These mutations affect only about 2% of ALS cases,
suggesting there are additional genetic contributors to be discovered.