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

Are presenilins intramembrane-cleaving proteases? Implications for the molecular mechanism of Alzheimer's disease.

  [ Not Yet Rated ]   [ Discuss This Article ]
By Wolfe MS, De Los Angeles J, Miller DD, Xia W, Selk • www.ProHealth.com • August 31, 1999


The amyloid-beta protein (Abeta) is strongly implicated in the pathogenesis of Alzheimer's disease. The final step in the production of Abeta from the amyloid precursor protein (APP) is proteolysis by the unidentified gamma-secretases. This cleavage event is unusual in that it apparently occurs within the transmembrane region of the substrate. Studies with substrate-based inhibitors together with molecular modeling and mutagenesis of the gamma-secretase cleavage site of APP suggest that gamma-secretases are aspartyl proteases that catalyze a novel intramembranous proteolysis.

This proteolysis requires the presenilins, proteins with eight transmembrane domains that are mutated in most cases of autosomal dominant familial Alzheimer's disease. Two conserved transmembrane aspartates in presenilins are essential for gamma-secretase activity, suggesting that presenilins themselves are gamma-secretases. Moreover, presenilins also mediate the apparently intramembranous cleavage of the Notch receptor, an event critical for Notch signaling and embryonic development.

Thus, if presenilins are gamma-secretases, then they are also likely the proteases that cleave Notch within its transmembrane domain. Another protease, S2P, involved in the processing of the sterol regulatory element binding protein, is also a multipass integral membrane protein which cleaves within or very close to the transmembrane region of its substrate.

Thus, presenilins and S2P appear to be members of a new type of polytopic protease with an intramembranous active site.

Source: Biochemistry 1999 Aug 31;38(35):11223-30

(Department of Pharmaceutical Sciences, University of Tennessee, Memphis 38163, USA. wolfe@cnd.bwh.harvard.edu)







Post a Comment

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

More Weight Loss than Any Other Discovery in Supplement History More Weight Loss than Any Other Discovery in Supplement History
Reversing Neurodegeneration with a New Magnesium Compound Reversing Neurodegeneration with a New Magnesium Compound
Herbal Rescue for High Blood Sugar Herbal Rescue for High Blood Sugar
Coping When Colds or Flu Catch Up with You Coping When Colds or Flu Catch Up with You
Fatigue & Fibro Fog: Could You Have a B-12 Deficiency? Fatigue & Fibro Fog: Could You Have a B-12 Deficiency?

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