We noted you are experiencing viewing problems
-
Check with your IT department that JWPlatform, JWPlayer and Amazon AWS & CloudFront are not being blocked by your network. The relevant domains are *.jwplatform.com, *.jwpsrv.com, *.jwpcdn.com, jwpltx.com, jwpsrv.a.ssl.fastly.net, *.amazonaws.com and *.cloudfront.net. The relevant ports are 80 and 443.
-
Check the following talk links to see which ones work correctly:
Auto Mode
HTTP Progressive Download Send us your results from the above test links at access@hstalks.com and we will contact you with further advice on troubleshooting your viewing problems. -
No luck yet? More tips for troubleshooting viewing issues
-
Contact HST Support access@hstalks.com
-
Please review our troubleshooting guide for tips and advice on resolving your viewing problems.
-
For additional help, please don't hesitate to contact HST support access@hstalks.com
We hope you have enjoyed this limited-length demo
This is a limited length demo talk; you may
login or
review methods of
obtaining more access.
Printable Handouts
Navigable Slide Index
- Introduction
- Neurodegenerative diseases with inclusion bodies
- Abnormal proteins rapidly degraded in cells
- 2012: anniversary for protein degradation discovery
- More anniversaries for important discoveries
- The ubiquitin-proteasome pathway
- Ubiquitin conjugation to protein substrates
- Ubiquitin ligases and neurological disease
- Recognition of misfolded proteins by CHIP
- Conditions that induce muscle wasting
- Ubiquitin ligases are involved in muscle atrophy
- Atrogin-1/2 knockouts reduces rate of atrophy
- The p97/VCP protein
- p97/VCP involvement in human diseases
- Pathways for protein degradation
- Autophagy
- Pathway to autophagy and muscle atrophy
- Returning to pathways for protein degradation
- The Nedd4 ubiquitin-ligase
- α-Synuclein is ubiquitinated by Nedd5
- Ubiquitination Nedd4 and C-terminal of α-synuclein
- Nedd4 over-expression in human neuroblastoma
- ESCRT pathway
- Different types of ubiquitin chains exist in vivo
- Nedd4 in pigmented neurons with lewy bodies
Topics Covered
- Neurodegenerative diseases with inclusion bodies associated with ubiquitin and proteasomes
- Abnormal proteins rapidly degraded in cells
- The ubiquitin-proteasome pathway
- Ubiquitin ligases important in neurological disease
- CHIP, Hsp70 and Hsp90
- Conditions that induce muscle wasting
- Ubiquitin ligases in muscles atrophy
- P97/VCP
- Autophagy
- The Nedd4 ubiquitin-ligase and α-Synuclein
- The ESCRT pathway
- Proteasomal VS. lysosomal degradation (K48 and K63-linked chains)
- Expression of Nedd4 in Lewy bodies
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Goldberg, A. (2014, October 7). Protein degradation and defense against neurodegenerative disease 1 [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 9, 2024, from https://doi.org/10.69645/AVEQ6503.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Alfred Goldberg has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Protein degradation and defense against neurodegenerative disease 1
Published on October 7, 2014
39 min
A selection of talks on Neuroscience
Transcript
Please wait while the transcript is being prepared...
0:00
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.
0:22
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.