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

On-and-off fasting helps fight obesity, study finds

16 Tips from 16 Years Sick

Fibromyalgia Fare Fit for All Seasons

New Study Shows Artificial Sweeteners Lead to Diabetes

Essential Oils — An Effective and Healthy Option to Treat Headaches

Higher vitamin D levels associated with less severe disease in NAFLD patients

Can Pomegranates Slow Aging?

Krill Oil: Make This Omega-3 Supplement Part of Your Health Regimen

How zinc helps fight esophageal cancer

What Benefits Can You Get From High-Quality Whey Protein?

 
Print Page
Email Article

Zebrafish (Danio rerio) presenilin promotes aberrant amyloid beta-peptide production and requires a critical aspartate residue for its function in amyloidogenesis.

  [ Not Yet Rated ]   [ Discuss This Article ]
By Leimer U, Lun K, Romig H, Walter J, Grunberg J, Br • www.ProHealth.com • October 12, 1999


Alzheimer's disease (AD) is characterized by the invariable accumulation of senile plaques composed of amyloid beta-peptide (Abeta). Mutations in three genes are known to cause familial Alzheimer's disease (FAD). The mutations occur in the genes encoding the beta-amyloid precursor protein (betaAPP) and presenilin (PS1) and PS2 and cause the increased secretion of the pathologically relevant 42 amino acid Abeta42.

We have now cloned the zebrafish (Danio rerio) PS1 homologue (zf-PS1) to study its function in amyloidogenesis and to prove the critical requirement of an unusual aspartate residue within the seventh putative transmembrane domain. In situ hybridization and reverse PCR reveal that zf-PS1 is maternally inherited and ubiquitously expressed during embryogenesis, suggesting an essential housekeeping function. zf-PS1 is proteolytically processed to produce a C-terminal fragment (CTF) of approximately 24 kDa similar to human PS proteins.

Surprisingly, wt zf-PS1 promotes aberrant Abeta42 secretion like FAD associated human PS1 mutations. The unexpected pathologic activity of wt zf-PS1 may be due to several amino acid exchanges at positions where FAD-associated mutations have been observed. The amyloidogenic function of zf-PS1 depends on the conserved aspartate residue 374 within the seventh putative transmembrane domain. Mutagenizing this critical aspartate residue abolishes endoproteolysis of zf-PS1 and inhibits Abeta secretion in human cells. Inhibition of Abeta secretion is accompanied by the accumulation of C-terminal fragments of betaAPP, suggesting a defect in gamma-secretase activity.

These data provide further evidence that PS proteins are directly involved in the proteolytic cleavage of betaAPP and demonstrate that this function is evolutionarily conserved.

Source: Biochemistry 1999 Oct 12;38(41):13602-9
PMID: 10521267, UI: 99452701

(Department of Molecular Biology, J5, Central Institute of Mental Health, 68159 Mannheim, Germany, Department of Neurobiology, University of Heidelberg, INF 364, 69120 Heidelberg, Germany, Department of Biological Research, Boehringer. )




Post a Comment

Featured Products From the ProHealth Store
Ultra ATP+, Double Strength Ultra EPA  - Fish Oil Optimized Curcumin Longvida®


Article Comments



Be the first to comment on this article!

Post a Comment


 
Optimized Curcumin Longvida with Omega-3

Featured Products

Vitamin D3 Extreme™ Vitamin D3 Extreme™
50,000 IU Vitamin D3 - Prescription Strength
Ultra ATP+, Double Strength Ultra ATP+, Double Strength
Get energized with malic acid & magnesium
Energy NADH™ 12.5mg Energy NADH™ 12.5mg
Improve Energy & Cognitive Function
FibroSleep™ FibroSleep™
The All-in-One Natural Sleep Aid

Natural Remedies

Dreaming of a Good Night's Sleep? Dreaming of a Good Night's Sleep?
Cell-Charging Compound Gives Steady Energy to Fibromyalgia & Chronic Fatigue Patients Cell-Charging Compound Gives Steady Energy to Fibromyalgia & Chronic Fatigue Patients
IBS, Crohn’s Disease, Colitis, and Other Digestive Disorders IBS, Crohn’s Disease, Colitis, and Other Digestive Disorders
The Guaifenesin Story: A centuries-old bark extract used for clearing the airways – now key to a popular FM symptom-reversal protocol The Guaifenesin Story: A centuries-old bark extract used for clearing the airways – now key to a popular FM symptom-reversal protocol
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