We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us
PURITAN MEDICAL

Download Mobile App




Pharmacoperone Treatment Restores Proper Function to Misfolded Proteins

By LabMedica International staff writers
Posted on 23 Dec 2013
A novel class of low molecular weight compounds has been identified that serves as a sort of scaffolding to restore the structure of misfolded proteins – such as those that characterize neurodegenerative diseases like Alzheimer's and Parkinson's – and allows the cell to return them to their site of normal activity.

Many diseases result from genetic mutations that cause protein misfolding. More...
It had been thought previously that misfolded proteins were intrinsically nonfunctional. Recent studies have found, however, that the cell's "quality control system" misroutes such proteins within the cell—most frequently to the endoplasmic reticulum (ER)— and they cease to function only because they are not situated in the correct location.

Investigators at Oregon Health & Science University (Portland, USA) have been working with a class of compounds known as pharmacological chaperones (or pharmacoperones, from "protein chaperone"). These small molecules enter cells and serve as molecular scaffolding in order direct misfolded mutant proteins to fold and route correctly within the cell.

Pharmacoperones correct the folding of misfolded proteins, allowing them to pass through the cell's quality-control system and become correctly routed. Since mutations often cause disease by causing misfolding and misrouting, pharmacoperones are potentially therapeutic agents, since they are able to correct this defect.

In a paper published in the December 9, 2013, online edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) the investigators described the use of a pharmacoperone to treat hypogonadotropic hypogonadism (failed puberty associated with low or apulsatile luteinizing hormone) caused by the recessive GnRHR E90K mutation in a mouse model.

They found that pulsatile pharmacoperone therapy restored E90K from ER retention to the plasma membrane, concurrently with responsiveness to its natural ligand, gonadotropin releasing hormone, and an agonist that is specific for the mutant. Spermatogenesis, proteins associated with steroid transport and steroidogenesis, and androgen levels were restored in mutant male mice following pharmacoperone therapy.

"These findings show how valuable laboratory animals are in identifying new treatments for human disease," said senior author Dr. P. Michael Conn, professor of physiology and pharmacology, cell biology and development, and obstetrics and gynecology at the Oregon Health & Science University. "We expect that these studies will change the way drug companies look for drugs, since current screening procedures would have missed many useful pharmacoperone drugs. The opportunity here is going to be enormous because so many human diseases are caused by misfolded proteins. The ability of these drugs to rescue misfolded proteins and return them to normalcy could someday be an underlying cure to a number of diseases. Drugs that act by regulating the trafficking of molecules within cells are a whole new way of thinking about treating disease."

Related Links:

Oregon Health & Science University





Gold Member
Antipsychotic TDM Assays
Saladax Antipsychotic Assays
Serological Pipet Controller
PIPETBOY GENIUS
New
PSA Assay
CanAg PSA EIA
New
Clostridium Difficile Toxin A+B Combo Card Test
CerTest Clostridium Difficile Toxin A+B
Read the full article by registering today, it's FREE! It's Free!
Register now for FREE to LabMedica.com and get access to news and events that shape the world of Clinical Laboratory Medicine.
  • Free digital version edition of LabMedica International sent by email on regular basis
  • Free print version of LabMedica International magazine (available only outside USA and Canada).
  • Free and unlimited access to back issues of LabMedica International in digital format
  • Free LabMedica International Newsletter sent every week containing the latest news
  • Free breaking news sent via email
  • Free access to Events Calendar
  • Free access to LinkXpress new product services
  • REGISTRATION IS FREE AND EASY!
Click here to Register








DIASOURCE (A Biovendor Company)

Channels

Molecular Diagnostics

view channel
Image: The discovery of early markers for ovarian cancer that would have improved sensitivity could aid detection (Photo courtesy of Adobe Stock)

Highly Accurate Biomarkers Could Detect Ovarian Cancer Before Clinical Diagnosis

Ovarian cancer is a deadly and challenging disease, primarily because early detection is difficult. Most women (70-75%) are diagnosed only after the cancer has already spread, which significantly reduces... Read more

Hematology

view channel
Image: CitoCBC is the world first cartridge-based CBC to be granted CLIA Waived status by FDA (Photo courtesy of CytoChip)

Disposable Cartridge-Based Test Delivers Rapid and Accurate CBC Results

Complete Blood Count (CBC) is one of the most commonly ordered lab tests, crucial for diagnosing diseases, monitoring therapies, and conducting routine health screenings. However, more than 90% of physician... Read more

Immunology

view channel
Image: CellLENS enables the potential precision therapy strategies against specific immune cell populations in the tissue environment (Photo courtesy of MIT)

New AI System Uncovers Hidden Cell Subtypes to Advance Cancer Immunotherapy

To produce effective targeted therapies for cancer, scientists need to isolate the genetic and phenotypic characteristics of cancer cells, both within and across different tumors. These differences significantly... Read more

Technology

view channel
Image: The Check4 gene-detection platform (Photo courtesy of IdentifySensors)

Electronic Biosensors Used to Detect Pathogens Can Rapidly Detect Cancer Cells

A major challenge in healthcare is the early and affordable detection of serious diseases such as cancer. Early diagnosis remains difficult due to the complexity of identifying specific genetic markers... Read more
Copyright © 2000-2025 Globetech Media. All rights reserved.