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

Can Autoimmune Conditions be Reversed? Researchers Make a Surprising Discovery

Scientifically-designed fasting diet lowers risks for major diseases

How One Tiny Molecule Turned into One Huge Health Breakthrough

Acupuncture boosts effectiveness of standard medical care for chronic pain, depression

Research on Astaxanthin Demonstrates Significant Whole Body Benefits

Humans have three times more brown body fat

Nutrients Boost Stem Cell Function

B12 Proven Essential for Every Cell

Soy isoflavones may benefit breast cancer patients

Dietary prebiotics improve sleep, buffer impacts of stress, says study

 
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
Ultra ATP+, Double Strength FibroSleep™ Optimized Curcumin Longvida®

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
Energy NADH™ 12.5mg Energy NADH™ 12.5mg
Improve Energy & Cognitive Function
Ultra EPA  - Fish Oil Ultra EPA - Fish Oil
Ultra concentrated source of essential fish oils
Optimized Curcumin Longvida® Optimized Curcumin Longvida®
Supports Cognition, Memory & Overall Health

Natural Remedies

Fatigue & Fibro Fog: Could You Have a B-12 Deficiency? Fatigue & Fibro Fog: Could You Have a B-12 Deficiency?
Restore Youthful Cognition and Well-Being Restore Youthful Cognition and Well-Being
Optimize Your Immune System Naturally: Thymic Protein A Optimize Your Immune System Naturally: Thymic Protein A
Magnesium + Malic Acid: One-Two Punch for Pain & Fatigue Magnesium + Malic Acid: One-Two Punch for Pain & Fatigue
Rejuvenating the Brain - How PQQ Helps Power Up Mental Processing Rejuvenating the Brain - How PQQ Helps Power Up Mental Processing

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