New study uncovers how brain cells degrade dangerous protein aggregates
Figure 1: Model for p62-mediated selective autophagy pathway. Credit: RIKEN
Researchers at the RIKEN Brain Science Institute (BSI) have discovered a key mechanism responsible for selectively degrading aggregates of ubiquitinated proteins from the cell. Their findings indicate that the capture and removal of such aggregates is mediated by the phosphorylation of a protein called p62, opening the door to new avenues for treating neurodegenerative diseases such as Huntington's disease and Alzheimer's disease.
One of the most important activities of a cell is the production of proteins, which play essential functions in everything from oxygen transport, to immune defense, to food digestion. Equally important to the cell's survival is how it deals with these proteins when they pass their expiry date: damaged or misfolded proteins have been associated with a range of debilitating conditions, including neurodegenerative diseases such as Alzheimer's disease.
In eukaryotic cells, the recycling of damaged or misformed proteins is governed by a small regulatory protein called ubiquitin in a process called "ubiquitination". By attaching itself to a protein, a ubiquitin molecule can tag the protein for destruction by proteasomes, large protein complexes that degrade and recycle unneeded proteins in the cell. This recycling of proteins by proteasomes is crucial to the maintenance of cellular homeostasis.
With their research, the BSI research group sought to shed light on one area where proteasome-based recycling falls short: protein complexes or aggregates, which proteasomes have trouble degrading. The group shows that this weakness is made up for by the phosphorylation of a protein called p62 at the serine 403 (S403) loci of its ubiquitin-associated (UBA) domain, which triggers a catabolic process called selective autophagy that degrades protein aggregates. It does this by forming a "sequestosome", a structure which sequesters polyubiquitinated protein aggregates in preparation for autophagy.
Published in the journal Molecular Cell, the discovery of this mechanism opens the door to the development of new, more effective drugs for selectively degrading protein aggregates, promising applications in the treatment of a range of neurodegenerative diseases.
Provided by RIKEN
- Self-digestion as a means of survival Feb 27, 2009 | not rated yet | 0
- Researchers identify novel mechanism for regulation of gene expression Sep 26, 2008 | not rated yet | 0
- Mutations that cause Parkinson's disease prevent cells from destroying defective mitochondria May 10, 2010 | not rated yet | 0
- Researchers identify enzyme that regulates degradation of damaged proteins Sep 27, 2011 | not rated yet | 0
- Neurodegeneration 'clumping proteins' common in aging process Aug 10, 2010 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
How can there be a term called "intestinal metaplasia" of stomach
8 hours ago Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
- More from Physics Forums - Medical Sciences
More news stories
Widely available in pharmacies and health stores, phosphatidylserine is a natural food supplement produced from beef, oysters, and soy. Proven to improve cognition and slow memory loss, it's a popular treatment for older ...
Medical research 3 hours ago | 5 / 5 (1) | 0 |
Researchers at Emory University have identified a protein that stimulates a pair of "orphan receptors" found in the brain, solving a long-standing biological puzzle and possibly leading to future treatments for neurological ...
Medical research 3 hours ago | not rated yet | 0 |
Australian scientists have charted the path of insulin action in cells in precise detail like never before. This provides a comprehensive blueprint for understanding what goes wrong in diabetes.
Medical research 4 hours ago | 4.5 / 5 (2) | 0 |
Researchers at the University of Illinois at Chicago College of Medicine will study gender differences in how the heart uses and stores fat—its main energy source—and how changes in fat metabolism play ...
Medical research 6 hours ago | not rated yet | 0
Nearly 20 percent of kidneys that are recovered from deceased donors in the U.S. are refused for transplant due to factors ranging from scarring in small blood vessels of the kidney's filtering units to the organ going too ...
Medical research 23 hours ago | 5 / 5 (2) | 0 |
Researchers at USC have found that a class of pharmaceuticals can both prevent and treat Alzheimer's Disease in mice.
1 hour ago | not rated yet | 0 |
Variation in the gene MUC5B among patients with idiopathic pulmonary fibrosis was associated with improved survival, according to a study published online by JAMA. The study is being released early online to coincide with i ...
11 minutes ago | not rated yet | 0
As many as 35 percent of Mexican young adults may have a genetic predisposition for obesity, said a University of Illinois scientist who conducted a study at the Universidad Autónoma de San Luis Potosί.
14 minutes ago | not rated yet | 0
A study of veterans at high risk for developing lung cancer shows that low-dose computed tomography (LDCT) can be highly effective in helping clinicians spot tiny lung nodules which, in a small number of patients, may indicate ...
8 minutes ago | not rated yet | 0
Among patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) requiring hospital admission, a 5-day glucocorticoid treatment course was non-inferior (not worse than) to a 14-day course with regard ...
8 minutes ago | not rated yet | 0
African-Americans are less likely than whites and women are more likely than men to have had a prior diagnosis of chronic obstructive pulmonary disease (COPD) regardless of their current disease severity, according to a new ...
9 minutes ago | not rated yet | 0