I'm Albee Messing from the University of Wisconsin in Madison.
Today I'm going to talk about astrocytes and
Alexander disease and how this disorder is the first,
but certainly not the last primary disorder of astrocytes.
Why is that of interest? There's currently a great deal of speculation regarding
the role that astrocytes play in neurodegenerative diseases such as Alzheimer's,
Parkinson's, Huntington's, and ALS.
What I'll argue today is that the clearest example of astrocytes being
the culprit in disease is the rare genetic disorder, Alexander disease,
and the extent to which we can understand how
astrocyte function is impaired in Alexander disease,
and the strategies we can devise to restore astrocyte function will have
significant implications for how we deal with
many more common neurological diseases that confront us.
The general overview of this problem is shown on this slide.
Thanks to advances made during the past 15 years,
we now know that Alexander disease is caused by
mutations in the astrocyte intermediate filament known as GFAP,
as shown on the left.
These are associated with the formation of
protein aggregates within the cytoplasm of astrocytes,
shown in the middle, and then ultimately with the brain pathology,
as shown on the right.
The real excitement in the field now is trying to understand these two steps;
how do the GFAP mutations lead to these protein aggregates,
and then secondly, how do these aggregates lead to
the catastrophic effects on the central nervous system?
This talk is divided into three parts.
In the first section, I'll make some general comments about
GFAP and discuss the clinical features,
the pathology, and the genetics of Alexander disease.
In the second section,
I'll discuss model systems for studying the disease, in particular,
mouse models, and what we've learned about the pathogenesis of the disorder.
Then finally, based largely on studies in cell culture and mouse model systems,
our ideas for developing therapies for Alexander disease.
GFAP has actually been known to neuroscientists for quite some time.