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My
name is Alfred Goldberg.
I'm a professor of Cell Biology
at Harvard Medical School.
And today I'd like to talk about
a fundamental cellular process,
in which all cells use to
keep alive but is particularly
important in our defenses against
neurodegenerative disease.
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Neurodegenerative diseases include
a number of the major challenges
that our society faces.
Parkinson's disease,
Huntington's disease
are the most common
neurodegenerative diseases--
amyotrophic lateral sclerosis,
different forms of dementia.
The common feature
of all these diseases
is that they're associated with
the accumulation in neurons
of a variety of aggregated proteins.
As shown in the next slide,
each of these diseases,
under the microscope, is associated
with the appearance in neurons
of inclusions of abnormal proteins
that appear with age in patients
and eventually trigger cell death.
The actual proteins that
accumulate in these aggregates
vary between the diseases-- Tau
in Alzheimer's, alpha-synuclein
in Parkinson's disease
and in Lewy body dementia,
superoxide dismutase in ALS.
And a variety of proteins with
extended glutamine reagents
are found in Huntington's
and related diseases.
What's of major interest is that
these inclusions are all associated
with a small protein ubiquitin
and portions of the proteasome.
These are the hallmarks
of the degradative process
that I would like to discuss today.
In fact, they're an indication
that the cells are trying, put
in the patient's, clearly failing to
eliminate these misfolded proteins.
It's now been known for 40 years
that all cells, from bacteria
to mammalian cells, rapidly degrade
misfolded or damaged proteins.
The next slide is a bit
of protein sociology.
It lists the kinds of proteins that
have been shown in various cells
to be selectively degraded.
