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

Vitamin D supplements, sleep could help manage pain

Bacopa: The Herb That May Increase Your Brain Power

Eat More Yogurt and Avoid Osteoporosis

Coffee, herbal tea may help prevent liver fibrosis

Crafty Uses for Carrot Seed Oil

Higher omega 3 levels linked to improved brain blood flow

Curcumin, resveratrol, ursolic acid show promise against prostate cancer

Olive oil compound could help protect against brain cancer

Probiotic use linked to improved symptoms of depression

How Fish Oil Benefits Heart Disease Patients with Depression

 
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
FibroSleep™ Vitamin D3 Extreme™ 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


 
NAD+ Ignite with Niagen

Featured Products

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 EPA  - Fish Oil Ultra EPA - Fish Oil
Ultra concentrated source of essential fish oils
Mitochondria Ignite™ with NT Factor® Mitochondria Ignite™ with NT Factor®
Reduce Fatigue up to 45%

Natural Remedies

Coenzyme Q10 - The Energy Maker Coenzyme Q10 - The Energy Maker
The Crucial Role CoQ10 Plays in Fibromyalgia and ME/CFS The Crucial Role CoQ10 Plays in Fibromyalgia and ME/CFS
The Big Blue Fish that Helps Chase the Blues Away The Big Blue Fish that Helps Chase the Blues Away
Running on Empty? Fuel Up with NADH Running on Empty? Fuel Up with NADH
How I Found My Long-Lost Energy How I Found My Long-Lost Energy

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