Natural Alzheimer's weapon suggests better treatment
Dr. Anil G. Cashikar (left) and Graduate Student Juhi Ojha have identified a natural mechanism for managing high levels of toxic amyloid beta peptide that occurs in Alzheimer's disease. Credit: Phil Jones/GHSU photograhper
Scientists have shown a molecular chaperone is working like a waste management company to collect and detoxify high levels of toxic amyloid beta peptide found in Alzheimer's disease.
It was known that the molecular chaperone, HspB1, was present in the hallmark plaque of Alzheimer's patients but its role remained a mystery.
"What we have found is HspB1 is a protective mechanism that tries to get rid of the toxic oligomers or aggregates of amyloid beta that occur in Alzheimer's," said Dr. Anil G. Cashikar, Biochemist at Georgia Health Sciences University's Center for Molecular Chaperones and Radiobiology. He is corresponding author of the study published in Molecular and Cellular Biology.
Amyloid beta peptide, or Abeta, is believed to start the cascade of events that leads to brain cell damage and death in Alzheimer's: as levels increase, the peptide starts clumping in the brain. In fact, high levels in the spinal fluid are a diagnostic marker for the disease. Molecular chaperones are known for their propensity to respond to disease-producing misfolded proteins, which is how the body views excessive Abeta.
While resulting plaques occupy prime real estate in the brain, it's still better than toxic Abeta killing neurons, Cashikar said. "We think maybe the system gets overwhelmed."
Acknowledging much work remains, the scientist is excited about identifying the protective mechanism and exploring its treatment potential.
Earlier this year, a paper Cashikar published in PLoS One showed deleting genes with a similar function from a mouse model of Alzheimer's worsened disease symptoms. The new study also showed neurons from HspB1-deficient mice were more sensitive to the toxic ravages of Abeta.
"HspB1 is present because its function is to protect cells. The implication is if we can elevate the levels of this molecular chaperone, we may be able to handle the situation a little better," Cashikar said.
He wants to exploit this natural system by developing a smaller version of the molecular chaperone that could be put into the bloodstream to leach excess Abeta from the brain. The brain has a natural protective mechanism that likely would prevent its direct application. However, the natural affinity of amyloid beta and HspB1 indicates a more distant approach could be effective. "We want to come up with smaller versions of HspB1 that can be put into the bloodstream so you can sop up the material from the brain into the blood where it can be cleared more efficiently." He also wants to explore a way to increase brain cells' natural production of protective HspB1.
Neurons actually also make the Abeta believed to attack them in Alzheimer's. The peptide's normal function in the brain is not clear, but early evidence suggests it could be involved in synaptic pruning, which is essential for memory formation. Synapses connect neurons and some existing connections must be cut for new connections and memories to be made. Why neurons start making too much Abeta and how its overproduction can be controlled are million-dollar questions, Cashikar said.
A related ongoing debate is whether the amyloid plaques and neurofibrillarly tangles, insoluble globs of protein also found in Alzheimer's, are a cause or result of the disease. Cashikar's work as well as new studies on the neurofibrillarly tangles, suggest both are protective mechanisms. Also, there is evidence of both in the brains of some healthy, elderly individuals.
GHSU Graduate Student Juhi Ojha is first author on the paper.
Provided by Georgia Health Sciences University
- Alzheimer's memory problems originate with protein clumps floating in the brain, not amyloid plaques Apr 27, 2010 | not rated yet | 0
- Peripheral induction of Alzheimer's-like brain pathology in mice Oct 21, 2010 | not rated yet | 0
- Naturally occurring enzyme can break down key part of Alzheimer's plaques Oct 24, 2006 | not rated yet | 0
- Neuroimaging study describes Alzheimer's disease-like changes in elderly people without the disease Mar 15, 2010 | not rated yet | 0
- APP -- Good, bad or both? Oct 18, 2009 | 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
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 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...
- More from Physics Forums - Medical Sciences
More news stories
By discovering the new mechanism by which estrogen suppresses lipid synthesis in the liver, UC Irvine endocrinologists have revealed a potential new approach toward treating certain liver diseases.
Medical research May 23, 2013 | 5 / 5 (1) | 0 |
Aortic arch pulse wave velocity, a measure of arterial stiffness, is a strong independent predictor of disease of the vessels that supply blood to the brain, according to a new study published in the June issue the journal ...
Medical research May 23, 2013 | not rated yet | 0
Since the discovery of Prontosil in 1932, sulfonamide antibiotics have been used to combat a wide spectrum of bacterial infections, from acne to chlamydia and pneumonia. However, their side effects can include serious neurological ...
Medical research May 23, 2013 | 3 / 5 (1) | 0 |
Scientists at the National Institutes of Health report they have discovered in mouse studies that a small molecule released in the spinal cord triggers a process that is later experienced in the brain as ...
Medical research May 23, 2013 | 5 / 5 (3) | 0 |
Spanish researchers have discovered that the daily clearance of neutrophils from the body stimulates the release of hematopoietic stem cells from the bone marrow into the bloodstream, according to a report published today ...
Medical research May 23, 2013 | 5 / 5 (2) | 0
Coenzyme Q10 decreases all cause mortality by half, according to the results of a multicentre randomised double blind trial presented today at Heart Failure 2013 congress. It is the first drug to improve heart failure mortality ...
4 hours ago | 5 / 5 (1) | 4
Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.
22 hours ago | 3.7 / 5 (3) | 3 |
Heart failure accelerates the aging process and brings on early andropausal syndrome (AS), according to research presented today at the Heart Failure Congress 2013. AS, also referred to as male 'menopause', was four times ...
4 hours ago | not rated yet | 1
Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...
20 hours ago | 3 / 5 (2) | 0 |
Biological processes are generally based on events at the molecular and cellular level. To understand what happens in the course of infections, diseases or normal bodily functions, scientists would need to ...
23 hours ago | 5 / 5 (5) | 0 |
(AP)—Department of Justice lawyers have again asked a federal appeals court in New York to delay lifting age restrictions and prescription requirements on an emergency contraceptive popularly known as the morning-after ...
3 hours ago | not rated yet | 0