RxPG News Feed for RxPG News

Medical Research Health Special Topics World
  Home
 
   Health
 Aging
 Asian Health
 Events
 Fitness
 Food & Nutrition
 Happiness
 Men's Health
 Mental Health
 Occupational Health
 Parenting
 Public Health
 Sleep Hygiene
 Women's Health
 
   Healthcare
 Africa
 Australia
 Canada Healthcare
 China Healthcare
 India Healthcare
 New Zealand
 South Africa
 UK
 USA
 World Healthcare
 
   Latest Research
 Aging
  Dementia
   Alzheimer's
  Parkinson's
 Alternative Medicine
 Anaethesia
 Biochemistry
 Biotechnology
 Cancer
 Cardiology
 Clinical Trials
 Cytology
 Dental
 Dermatology
 Embryology
 Endocrinology
 ENT
 Environment
 Epidemiology
 Gastroenterology
 Genetics
 Gynaecology
 Haematology
 Immunology
 Infectious Diseases
 Medicine
 Metabolism
 Microbiology
 Musculoskeletal
 Nephrology
 Neurosciences
 Obstetrics
 Ophthalmology
 Orthopedics
 Paediatrics
 Pathology
 Pharmacology
 Physiology
 Physiotherapy
 Psychiatry
 Radiology
 Rheumatology
 Sports Medicine
 Surgery
 Toxicology
 Urology
 
   Medical News
 Awards & Prizes
 Epidemics
 Launch
 Opinion
 Professionals
 
   Special Topics
 Ethics
 Euthanasia
 Evolution
 Feature
 Odd Medical News
 Climate

Last Updated: Oct 11, 2012 - 10:22:56 PM
Alzheimer's Channel

subscribe to Alzheimer's newsletter
Latest Research : Aging : Dementia : Alzheimer's

   EMAIL   |   PRINT
Amyloid plaques and neurofibrillary tangles are mere markers, not cause of Alzheimer’s disease

Feb 15, 2007 - 3:20:03 AM , Reviewed by: Dr. Ankush Vidyarthi
"Recent scientific discoveries indicate that these large, insoluble aggregates might merely be markers of the disease –– they do not cause the disease. Rather, smaller soluble oligomers, or peptide complexes, are now felt to be the causative agents, and I find that very interesting.”

 
[RxPG] A completely new approach to the study of Alzheimer’s disease, initiated by a professor at the University of California, Santa Barbara, may solve a critical piece in the puzzle of the disease. This tragic neurological illness progressively erases memory in its millions of victims. The key to the new approach is understanding the way certain proteins in the brain fold, or rather “misfold.”

Michael Bowers, a professor in the Department of Chemistry and Biochemistry, developed this project, which is being funded by the National Institutes of Health. Bowers’s laboratory will receive $1.3 million of the total $9 million project grant, plus biological samples worth an additional $500,000. The grant covers a five-year period. Four institutions are involved.

Bowers is using specialized chemical research methods and applying them to biology. His research will depend upon the study of rare peptides, or strings of amino acids, that are difficult to produce. These will be provided by co-investigator David Teplow, a professor at UCLA’s David Geffen School of Medicine, who has been involved in Alzheimer’s research for over 10 years. Joan-Emma Shea, also a professor in UCSB’s Department of Chemistry and Biochemistry, heads the theoretical modeling aspect of the project.

“Until about five or six years ago, everyone assumed that the large amyloid plaques, or neurofibrillary tangles, that were found in the brains of Alzheimer’s victims were the cause of the disease,” said Bowers. “However, recent scientific discoveries indicate that these large, insoluble aggregates might merely be markers of the disease –– they do not cause the disease. Rather, smaller soluble oligomers, or peptide complexes, are now felt to be the causative agents, and I find that very interesting.”

He explained that now the hunt is on for the “small stuff.” Because of their expertise in certain chemical methodologies, Bowers and his research group are able to track down the molecular level changes that lead to development of the disease.

The process of aggregation of proteins that cause the plaque begins in a way that Bowers has begun to clarify. The goal is to find non-toxic drugs that will interrupt the aggregation process. “If we can do that, we can stop the disease,” said Bowers. “However, once you start losing neurons, things become very difficult, because the body doesn’t readily replace them due to their very large size. If we could find a marker, early on, to indicate when the patient first has the disease, then the new drug or drugs that we hope to develop could prevent further damage.”

Bowers described his approach as a whole new way to determine the structure and composition of the Abeta 42 peptide and its oligomers that are primarily responsible for Alzheimer’s disease. The research team is analyzing the way this peptide folds, causing it to aggregate and disrupt neuronal function.

“In biology, structure and function are tightly coupled,” said Bowers. “When it became clear that small soluble oligomers were most probably the toxic agents, I realized our ion mobility methods could contribute, since we could measure the oligomer distribution and shapes of these peptides for the first time.”

Three years of preliminary work convinced the National Institutes of Health to provide funding. “In the last several months, I believe we have uncovered the identity and shape of the primary toxic oligomer,” said Bowers. “Our results are consistent with findings on transgenic mice, recently published in the journal Nature, indicating that soluble oligomers with masses matching those we have identified have been extracted from the brains of the diseased animals.”

The transgenic mice that Bowers refers to are laboratory mice that have had the gene that creates the Abeta 42 precursor protein spliced into their genome. This process has been shown experimentally to produce memory loss in the animals.

The key aspect of ion mobility is its ability to measure accurate cross sections of complex aggregations of proteins and obtain information on their three-dimensional shape. When coupled with mass spectrometry, electrospray ionization, and high-level molecular modeling, it becomes a very powerful technique.

The experiment starts with electrospray ionization, a method of spraying the solution containing the peptides of interest into fine droplets and then letting the droplets evaporate. Following evaporation, mass spectrometry is employed to determine the mass or weight of the species that were in the solution, and from that to determine the composition. Finally ion mobility is used to show the shape of the Abeta 42 peptide and its oligomers.

“Our experimental and theoretical methods allow us to investigate structure, aggregation, and energetics in a variety of protein systems,” said Bowers. “In addition, we are able to explore correlations between solution and gas phase protein structures, learning that in many critical cases, these structures are very similar.”

The experimental methodology for the Alzheimer’s study was developed at UCSB 15 years ago, in studies involving “buckyballs.” Buckyball is the nickname for the versatile carbon molecule known as C60, which scientists named “buckminsterfullerene” after American architect R. Buckminster Fuller, who designed geodesic domes in a soccer-ball shape. “Our ion mobility and mass spectrometry methods provide a new way to attack the molecular basis of neurological diseases that has not been explored until now,” said Bowers.

Bowers and his group are currently investigating proteins involved in the study of several neurological diseases. Besides Alzheimer’s disease, they are studying Parkinson’s disease and the various transmissible spongiform encephalopathies or “prion” diseases. In this latter case Bowers is receiving funding from the British government to find an ante-mortem test for the bovine prion disease usually called “mad cow” disease. The same test, if successful, should also work on deer and elk; an epidemic in the Midwestern United States now affects these animals.



On the web: http://www.ucsb.edu/ 

Advertise in this space for $10 per month. Contact us today.


Related Alzheimer's News


Subscribe to Alzheimer's Newsletter

Enter your email address:


 About Dr. Ankush Vidyarthi
This news story has been reviewed by Dr. Ankush Vidyarthi before its publication on RxPG News website. Dr. Ankush Vidyarthi, MBBS is a senior editor of RxPG News. He is also managing the marketing and public relations for the website. In his capacity as the senior editor, he is responsible for content related to mental health and psychiatry. His areas of special interest are mass-media and psychopathology.
RxPG News is committed to promotion and implementation of Evidence Based Medical Journalism in all channels of mass media including internet.
 Additional information about the news article
Besides Teplow and Shea, co-investigators on the Alzheimer’s project include Gal Bitan, assistant professor at UCLA’s David Geffen School of Medicine; Eugene Stanley, physics professor at Boston University; and, George Benedek, physics professor at MIT.
 Feedback
For any corrections of factual information, to contact the editors or to send any medical news or health news press releases, use feedback form

Top of Page

 
Contact us

RxPG Online

Nerve

 

    Full Text RSS

© All rights reserved by RxPG Medical Solutions Private Limited (India)