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

Is Coconut Oil Healthy? (The American Heart Association Doesn’t Think So)

American Heart Association Renders Itself Obsolete With 1960s Dietary Advice on Coconut Oil

Ginger Fights Obesity

Health Benefits of Artichokes

Putting the Spotlight on Coriander Seed Oil

Migraines? Powdered Ginger May Help

Are Americans Really Getting Too Much Vitamin D? A Critical Look at Recent Media Warnings

Eating more vegetable protein may protect against early menopause

Vitamin C and antibiotics: A new one-two 'punch' for knocking-out cancer stem cells

German Chamomile Oil: A Versatile Essential Oil You Should Have at Home

 
Print Page
Email Article

Cellular mechanisms of beta-amyloid production and secretion.

  [ 6 votes ]   [ Discuss This Article ]
By Sinha S, Lieberburg I • www.ProHealth.com • September 28, 1999


The major constituent of senile plaques in Alzheimer's disease is a 42-aa peptide, referred to as beta-amyloid (Abeta). Abeta is generated from a family of differentially spliced, type-1 transmembrane domain (TM)-containing proteins, called APP, by endoproteolytic processing. The major, relatively ubiquitous pathway of APP metabolism in cell culture involves cleavage by alpha-secretase, which cleaves within the Abeta sequence, thus precluding Abeta formation and deposition.

An alternate secretory pathway, enriched in neurons and brain, leads to cleavage of APP at the N terminus of the Abeta peptide by beta-secretase, thus generating a cell-associated beta-C-terminal fragment (beta-CTF). A pathogenic mutation at codons 670/671 in APP (APP "Swedish") leads to enhanced cleavage at the beta-secretase scissile bond and increased Abeta formation.

An inhibitor of vacuolar ATPases, bafilomycin, selectively inhibits the action of beta-secretase in cell culture, suggesting a requirement for an acidic intracellular compartment for effective beta-secretase cleavage of APP. beta-CTF is cleaved in the TM domain by gamma-secretase(s), generating both Abeta 1-40 (90%) and Abeta 1-42 (10%). Pathogenic mutations in APP at codon 717 (APP "London") lead to an increased proportion of Abeta 1-42 being produced and secreted. Missense mutations in PS-1, localized to chromosome 14, are pathogenic in the majority of familial Alzheimer's pedigrees.

These mutations also lead to increased production of Abeta 1-42 over Abeta 1-40. Knockout of PS-1 in transgenic animals leads to significant inhibition of production of both Abeta 1-40 and Abeta 1-42 in primary cultures, indicating that PS-1 expression is important for gamma-secretase cleavages. Peptide aldehyde inhibitors that block Abeta production by inhibiting gamma-secretase cleavage of beta-CTF have been discovered.

Source: Proc Natl Acad Sci U S A 1999 Sep 28;96(20):11049-53
PMID: 10500121, UI: 99432177

(Elan Pharmaceuticals, South San Francisco, CA 94080, USA. ssinha@elanpharma.com)







Post a Comment

Featured Products From the ProHealth Store
Mitochondria Ignite™ with NT Factor® FibroSleep™ Ultra EPA  - Fish Oil

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

Optimized Curcumin Longvida® Optimized Curcumin Longvida®
Supports Cognition, Memory & Overall Health
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

Natural Remedies

Pioneer Scientists Uncover a Revolutionary Neuroprotective Supplement for Nerve Health Pioneer Scientists Uncover a Revolutionary Neuroprotective Supplement for Nerve Health
How to Jump-start and Sustain Energy Production in CFS How to Jump-start and Sustain Energy Production in CFS
Natural Support for Mood, Sleep and Mental Focus? L-theanine Natural Support for Mood, Sleep and Mental Focus? L-theanine
Strengthen Cell Function with Energy-Boosting Niagen Strengthen Cell Function with Energy-Boosting Niagen
Running on Empty? Fuel Up with NADH Running on Empty? Fuel Up with NADH

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