ProHealth health Vitamin and Natural Supplement Store and Health
Home  |  Log In  |  My Account  |  View Cart  View Your ProHealth Vitamin and Supplement Shopping Cart
800-366-6056  |  Contact Us  |  Help
Facebook Google Plus
Fibromyalgia  Chronic Fatigue Syndrome & M.E.  Lyme Disease  Natural Wellness  Supplement News  Forums  Our Story
Store     Brands   |   A-Z Index   |   Best Sellers   |   New Products   |   Deals & Specials   |   Under $10   |   SmartSavings Club

Trending News

10 Fibro-Friendly Foods with a Bonus: Beautiful Skin

Studies Show that Magnesium L-threonate Improves Brain Plasticity, Leading to Direct and Significant...

Clary Sage Oil May Be Pricey, but Its Benefits Are Priceless

Pumpkin Pie Turmeric Breakfast Smoothie - Vegan + Gluten-Free

Component of red wine, grapes can help to reduce inflammation, study finds

Poly MVA: A Novel Therapy for Increasing Energy, Repairing DNA, and Promoting Overall Health

Vitamin D supplementation extends life in mouse model of Huntington's disease

Omega-3 fatty acid stops known trigger of lupus

Conquer Your Email Inbox, Increase Productivity and Reduce Stress

The Significance of Selenium

Print Page
Email Article

Scripps scientists discover new approach for treating 'misfolding diseases'

  [ 22 votes ]   [ Discuss This Article ] • January 30, 2003

Professor Jeffery W. Kelly, Ph.D., and his colleagues in the Department of Chemistry and The Skaggs Institute for Chemical Biology at The Scripps Research Institute (TSRI) have demonstrated a new approach for treating "amyloid" diseases--particularly transthyretin amyloid diseases, which are similar to Parkinson's and Alzheimer's.

These amyloid diseases are caused by proteins misfolding into a structure that leads them to cluster together, forming microscopic fibril plaques made up of hundreds of these misfolded proteins. The plaques deposit in internal organs and interfere with normal function, sometimes lethally. In the current issue of the journal Science, Kelly and his TSRI colleagues demonstrate the efficacy of using small molecules to stabilize the normal "fold" of transthyretin, preventing this protein from misfolding. Using this method, researchers were able to inhibit the formation of fibrils by a mechanism that is known to ameliorate disease.

"I'm very excited about pursuing these potential therapeutic opportunities," says Kelly, the report's lead author. Kelly is the Lita Annenberg Hazen Professor of Chemistry in The Skaggs Institute for Chemical Biology and vice president of academic affairs at TSRI.

Misfolding Causes Disease

Familial amyloid polyneuropathy (FAP) is a collection of over 80 rare amyloid diseases caused by the misfolding of the protein transthyretin (TTR), which the liver secretes into the bloodstream to carry thyroid hormone and vitamin A. Normally, TTR circulates in the blood as an active "tetramer" made up of four separate copies, or protein subunits, that bind to each other.

These tetramers, normally composed of identical protein subunits, come from two different genes. When one of the genes has a heritable defect, hybrid tetramers form that are composed of mutant and normal subunits. The inclusion of mutated subunits makes the tetramer less stable and causes the four subunits to more easily dissociate. Once the subunits are free, they misfold and reassemble into the hair-like amyloid fibrils.These fibrils cause the disease FAP by building up around peripheral nerve and muscle tissue, disrupting their function and leading to numbness, muscle weakness, and--in advanced cases--failure of the autonomic nervous system including the gastrointestinal tract. The current treatment for FAP is a liver transplant, which replaces the mutant gene with a normal copy.

An analogous disease called familial amyloid cardiomyopathy (FAC) causes fibril formation in the heart, which leads to cardiac dysfunction. About one million African-Americans carry the gene that predisposes them to FAC. Another amyloid disease affecting the heart, Senile Systemic Amyloidosis (SSA), afflicts an estimated 10 to 15 percent of all Americans over the age of 80.

Some therapeutic approaches that have previously been tried involve administering drugs that inhibit the growth of fibrils from the misfolded state. However, this often proves ineffective because fibril formation is strongly favored once an initial, misfolded "seed" fibril forms.

Kelly's approach is to prevent amyloid formation by stabilizing the native state of proteins--keeping them folded in their proper form. Instead of preventing the misfolded protein subunits from conglomerating to form plaques, he is attempting to prevent them from becoming abnormal monomeric subunits in the first place--by stabilizing the tetrameric "native state" of the protein.

Stabilization through Binding

Last year, Kelly and his colleagues discovered that TTR tetramers composed of both disease-associated and suppressor subunits ameliorate disease by stabilizing the tetramer, thus preventing the disease-associated subunits from contributing to fibril formation. They found that even one such suppressor subunit incorporated into a tetramer otherwise composed of disease-associated subunits doubles its stability.

"The suppressor TTR subunits prevent misfolding by blocking tetramer dissociation accomplished by raising the barrier associated with this process," says Kelly.

In the current study, Kelly and his found that the mechanism by which small molecules inhibit amyloidogenesis is analogous to the mechanism by which trans-suppression prevents disease--both increase the barrier associated with misfolding. The small molecules bind to the TTR protein and stabilize the tetramer, making it harder for the subunits to dissociate. Since trans-suppression is known to prevent disease onset in humans, there is good reason to be optimistic that the small molecule approach will be effective in humans.

"The same approach may also work with other amyloid diseases," says Kelly. "Any protein that misfolds and causes pathology that interacts with another protein or has a small molecule binding site could, in principle, be targeted [with a trans-suppression approach or a small molecule strategy to treat disease]."

The article, "Prevention of Transthyretin Amyloid Disease by Changing Protein Misfolding Energies" is authored by Per Hammarstrom, R. Luke Wiseman, Evan T. Powers, and Jeffery W. Kelly and appears in the January 31, 2003 issue of the journal Science.

The research was funded in part by the National Institutes of Health, TSRI’s Skaggs Institute for Chemical Biology, the Lita Annenberg Hazen Foundation, and through a postdoctoral fellowship sponsored by the Wenner-Gren Foundation.

Post a Comment

Featured Products From the ProHealth Store
Ultra ATP+, Double Strength Ultra EPA  - Fish Oil Mitochondria Ignite™ with NT Factor®

Looking for Vitamins, Herbs and Supplements?
Search the ProHealth Store for Hundreds of Natural Health Products

Article Comments

Be the first to comment on this article!

Post a Comment

Natural Pain Relief Supplements

Featured Products

FibroSleep™ FibroSleep™
The All-in-One Natural Sleep Aid
Optimized Curcumin Longvida® Optimized Curcumin Longvida®
Supports Cognition, Memory & Overall Health
Vitamin D3 Extreme™ Vitamin D3 Extreme™
50,000 IU Vitamin D3 - Prescription Strength
Energy NADH™ 12.5mg Energy NADH™ 12.5mg
Improve Energy & Cognitive Function
Ultra ATP+, Double Strength Ultra ATP+, Double Strength
Get energized with malic acid & magnesium

Natural Remedies

The Revolutionary 'Good Fat' That Promotes Heart, Brain, Bone and Joint Health The Revolutionary 'Good Fat' That Promotes Heart, Brain, Bone and Joint Health
Coping When Colds or Flu Catch Up with You Coping When Colds or Flu Catch Up with You
The New Dual Activation Pain Relief Cream The New Dual Activation Pain Relief Cream
Three-Step Strategy to Reverse Mitochondrial Aging Three-Step Strategy to Reverse Mitochondrial Aging
Fatigue & Fibro Fog: Could You Have a B-12 Deficiency? Fatigue & Fibro Fog: Could You Have a B-12 Deficiency?

ProHealth, Inc.
555 Maple Ave
Carpinteria, CA 93013
(800) 366-6056  |  Email

· Become a Wholesaler
· Vendor Inquiries
· Affiliate Program
Credit Card Processing
Be the first to know about new products, special discounts and the latest health news. *New subscribers only

CONNECT WITH US ProHealth on Facebook  ProHealth on Twitter  ProHealth on Pinterest  ProHealth on Google Plus

© 2016 ProHealth, Inc. All rights reserved. Pain Tracker App  |  Store  |  Customer Service  |  Guarantee  |  Privacy  |  Contact Us  |  Library  |  RSS  |  Site Map