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

Scientifically-designed fasting diet lowers risks for major diseases

More evidence for calorie restriction’s longevity effect

Supplementation with vitamin D associated with improved testosterone, erectile function among middle...

A Little Zinc Goes a Long Way

Vitamin D deficiency increases risk of chronic headache

VIDEO: The Best Brain Foods That Help Increase Your Memory!

Get the Most From Your Green Tea

Iron (And More) For Lasting, Natural Energy

Metabolic syndrome increases the need for vitamin E

Supplement combo improves bone density, mood, in postmenopausal women

 
Print Page
Email Article

Research Finds Alzheimer's Protein Jams Mitochondria of Affected Cells

  [ 62 votes ]   [ Discuss This Article ]
www.ProHealth.com • April 16, 2003


Opening a new front in the battle against Alzheimer's disease, scientists at the University of Pennsylvania have found that a protein long associated with the disease inflicts grave damage in a previously unimagined way: It seals off mitochondria in affected neurons, resulting in an "energy crisis" and buildup of toxins that causes cells to die. This pathway, the first specific biochemical explanation for pathologies associated with Alzheimer's, is detailed in the April 14 issue of the Journal of Cell Biology.

While the normal function of the amyloid precursor protein (APP) remains unknown, senior author Narayan G. Avadhani and his colleagues have determined that a mere 50-amino-acid stretch of the protein wreaks havoc by essentially starving mitochondria and the cells they nourish.

"We found that when APP leaves the nucleus, it can be directed both to mitochondria and to the endoplasmic reticulum," said Avadhani, professor of biochemistry and chair of the Department of Animal Biology in Penn's School of Veterinary Medicine. "APP has an acidic, negatively charged region that causes it to jam irreversibly while traversing protein transport channels in the mitochondrial membrane. This hampers, and eventually completely blocks, mitochondria's ability to import other proteins and produce cellular energy."

As if suffocating the cell's power plant weren't enough, jammed APP proteins also damaged the mouse neurons studied by Avadhani and co-author Hindupur K. Anandatheerthavarada in a second way. The end of the protein left dangling outside the mitochondrion contains a toxic product called A-Beta. The Penn researchers found that this toxin, a known component of the brain plaques and tangles that are a hallmark of Alzheimer's, is cleaved from the rest of the immobilized protein and accumulates in the cell.

"Researchers have observed many biochemical and biophysical phenomena associated with Alzheimer's disease," said Anandatheerthavarada, research assistant professor of biochemistry and the paper's first author, "but it has remained unclear whether these are causes of Alzheimer's or merely side effects. The pathway we observed, which leads directly to common symptoms, is the first with a demonstrated ability to cause the neuronal death associated with Alzheimer's disease."

The results are consistent with the progressive nature of Alzheimer's and other neurodegenerative diseases, the scientists said. As pores in the mitochondrial membrane clog with proteins -- inaccessible to enzymes that might normally degrade them -- cellular function is steadily and inevitably reduced until cell death, reached when APP succeeds in suffocating all the cell's mitochondria.

Avadhani and Anandatheerthavarada's results put a dent in cell biology dogma, which holds that each of the proteins produced in the nucleus can be directed to only one location in the cell. In APP's case, the Penn scientists have shown the targeting sequence within the protein's N-terminal directs it to at least two locations, the mitochondrion and endoplasmic reticulum.

The implication of mitochondrial failure is unexpected because most Alzheimer's researchers, believing the mitochondrion was not on APP's itinerary, have focused on the protein's effects on other organelles. In fact, Avadhani and Anandatheerthavarada found that mitochondria appear to be the only organelles whose membranes have trouble handling APP.

It remains unclear whether APP gets stuck in mitochondria's protein entryways because of its negative charge or bulkiness attributable to improper protein folding. Avadhani and Anandatheerthavarada plan to study the question, which could eventually yield medications to correct the problem.

"A mutant version of APP without the region that's prone to jamming passes into the mitochondria without a hitch," Avadhani said. "This suggests that pharmaceuticals could be developed to fix this domain, either by neutralizing its charge or folding it more tightly."



Post a Comment

Featured Products From the ProHealth Store
Optimized Curcumin Longvida® Mitochondria Ignite™ with NT Factor® FibroSleep™

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


 
NAD+ Ignite with Niagen

Featured Products

FibroSleep™ FibroSleep™
The All-in-One Natural Sleep Aid
Mitochondria Ignite™ with NT Factor® Mitochondria Ignite™ with NT Factor®
Reduce Fatigue up to 45%
Energy NADH™ 12.5mg Energy NADH™ 12.5mg
Improve Energy & Cognitive Function
Optimized Curcumin Longvida® Optimized Curcumin Longvida®
Supports Cognition, Memory & Overall Health
Ultra EPA  - Fish Oil Ultra EPA - Fish Oil
Ultra concentrated source of essential fish oils

Natural Remedies

A Hard-Working Molecule that May Help Ease Pain & Brighten Mood A Hard-Working Molecule that May Help Ease Pain & Brighten Mood
Everything You Always Wanted to Know About Sleep But Were Too Tired to Ask Everything You Always Wanted to Know About Sleep But Were Too Tired to Ask
Physically and Mentally Exhausted? How to Restore Energy at Its Source Physically and Mentally Exhausted? How to Restore Energy at Its Source
The Surprising Benefits of Probiotics - What You Didn't Know The Surprising Benefits of Probiotics - What You Didn't Know
Top 3 Nutrients to Detox the Liver and Soothe Digestion Top 3 Nutrients to Detox the Liver and Soothe Digestion

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

· Become a Wholesaler
· Vendor Inquiries
· Affiliate Program
SHOP WITH CONFIDENCE
Credit Card Processing
SUBSCRIBE TO OUR NEWSLETTERS
Get the latest news about Fibromyalgia, M.E/Chronic Fatigue Syndrome, Lyme Disease and Natural Wellness

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

© 2017 ProHealth, Inc. All rights reserved. Pain Tracker App  |  Store  |  Customer Service  |  Guarantee  |  Privacy  |  Contact Us  |  Library  |  RSS  |  Site Map