Corporate Banner
Satellite Banner
Cell Culture
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Understanding a Protein’s Role in Familial Alzheimer’s

Published: Monday, November 18, 2013
Last Updated: Monday, November 18, 2013
Bookmark and Share
Researchers have used genetic engineering of human iPSC’s to specifically and precisely parse the roles of a key mutated protein in causing familial Alzheimer's disease (AD).

The findings, published online in the journal Cell Reports, could help elucidate the still-mysterious mechanisms of Alzheimer's disease and better inform development of effective drugs, said principal investigator Lawrence Goldstein, PhD, professor in the Departments of Cellular and Molecular Medicine and Neurosciences and director of the UC San Diego Stem Cell Program.

"In some ways, this is a powerful technical demonstration of the promise of stem cells and genomics research in better understanding and ultimately treating AD," said Goldstein, who is also director of the new Sanford Stem Cell Clinical Center at UC San Diego. "We were able to identify and assign precise limits on how a mutation works in familial AD. That's an important step in advancing the science, in finding drugs and treatments that can slow, maybe reverse, the disease's devastating effects."

Familial AD is a subset of early-onset Alzheimer's disease that is caused by inherited gene mutations. Most cases of Alzheimer's disease — there are an estimated 5.2 million Americans with AD — are sporadic and do not have a precise known cause, though age is a primary risk factor.

In their study, Goldstein and colleagues examined presenilin 1 (PS1), a protein that helps break down other proteins, which is a vital biological necessity for cells and for life. Most notably, PS1 is the catalytic or action-driving component of gamma-secretase, an enzyme that cleaves or splits type-1 transmembrane proteins used to transport cellular material from one side of a cell's membrane to the other, from inside to outside or vice versa.

Among the type-1 proteins cleaved by gamma-secretase is amyloid precursor protein or APP, whose function remains incompletely known. When APP is cleaved by gamma-secretase, peptide fragments called amyloid beta are created. Some researchers believe the accumulation of certain kinds of amyloid beta may result in neuron-killing plaques in the brain, a consequence that has been strongly linked to the development of AD.

Ordinarily, the "molecular scissors" of PS1 do their cutting with no adverse effect, according to Goldstein. But perhaps 20 percent of the time, he said there are "bad cuts" that result in potentially harmful amyloid beta fragments. "Our research demonstrates very precisely that mutations in PS1 double the frequency of bad cuts," he said.

The researchers achieved their unprecedented precision by generating differentiated, purified neurons from stem cells derived from noted biologist Craig Venter, whose genome was fully sequenced and released for public research use in 2007. The created neurons contained different alleles or forms of the mutated gene that produces PS1.

"We were able to investigate exactly how specific mutations and their frequency change the behavior of neurons," said Goldstein. "We took finely engineered cells that we knew and understood and then looked how a single mutation caused changes in the molecular scissors and what happened next."

To exclude potential off-target artifacts observed in previous genome editing work, study co-author Kun Zhang, PhD, associate professor in the Department of Bioengineering at UC San Diego, said he and colleagues used whole exome sequencing to compare the engineered cells with other control cells. They determined that their genome editing approach did not introduce any additional mutations.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,900+ scientific posters on ePosters
  • More than 4,200+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Cellular “ORACLs” to Aid Drug Discovery
New approach for finding therapeutics is inspired by face-recognition software.
Wednesday, December 16, 2015
Artificial Kidney Research Gets A Boost
Development of a surgically implantable, artificial kidney — a promising alternative to kidney transplantation or dialysis for people with end-stage kidney disease — has received a $6 million boost.
Monday, November 09, 2015
Growing Spinal Disc Tissue
Scientists develop new method for growing spinal disc tissue in the lab for combating chronic back pain.
Friday, July 03, 2015
May the Cellular Force be With You
Like tiny construction workers, cells sculpt embryonic tissues and organs in 3D space.
Friday, December 13, 2013
Developmental Protein Plays Role in Spread of Cancer
A protein used by embryo cells during early development, and recently found in many different types of cancer, apparently serves as a switch regulating metastasis.
Tuesday, June 18, 2013
Nobel Prize Winner Yamanaka Remains at Forefront of Fast-Moving Stem Cell Field
Shinya Yamanaka, MD, PhD, named winner of the 2012 Nobel Prize for Physiology or Medicine, said he was doing some housecleaning when the call came in, and was “very surprised.”
Friday, October 12, 2012
Well-known Protein Reveals New Tricks
A protein called "clathrin," which is found in every human cell and plays a critical role in transporting materials within them, also plays a key role in cell division.
Friday, September 07, 2012
Protein Build-up Leads to Neurons Misfiring
New evidence shows that alpha-synuclein protein build-up inside neurons causes them to not only become "leaky," but also to misfire due to calcium fluxes.
Friday, July 20, 2012
Scientific News
Mitochondria Shown to Trigger Cell Ageing
An international team of scientists has for the first time shown that mitochondria, the batteries of the cells, are essential for ageing.
Cancer Cells Kill Off Healthy Neighbours
Cancer cells create space to grow by killing off surrounding healthy cells, according to UK researchers working with fruit flies.
Editing of Embryos Approved in the UK
The Human Fertilisation and Embryology Authority (HFEA) has approved a research application from the Francis Crick Institute to use new "gene editing" techniques on human embryos.
Microbes Take Their Vitamins
Scientists exploit organisms' needs in order to track 'vitamin mimics' in bacteria.
Machine Learning Uncovers Unknown Bacterial Features
Technique robustly identified characteristic gene expression patterns in response to antibiotics, low oxygen conditions.
CRISPR-Cas9 Gene Editing Advances Again
UC Berkeley researchers have made a major improvement in CRISPR-Cas9 technology that achieves an unprecedented success rate of 60 percent when replacing a short stretch of DNA with another.
Disrupting Cell’s Supply Chain Freezes Cancer Virus
When the cancer-causing Epstein-Barr virus moves into a B-cell of the human immune system, it tricks the cell into rapidly making more copies of itself, each of which will carry the virus.
Why Do Some Infections Persist?
In preparing for the possibility of an antibiotic onslaught, some bacterial cultures adopt an all-for-one/one-for-all strategy that would make a socialist proud, University of Vermont researchers have found.
ASCB: A CELLebration of Cell Biology
The last major congress of the year, ASCB is less a platform for launching new products, but one for confirming and consolidating the trends that have emerged over the past 12 months.
Squeezing Cells into Stem Cells
EPFL scientists have developed a new method that helps cells turn in usable stem cells. The new approach involves “squeezing” cells with a gel, and paves the way for large-scale production of stem cells for medical purposes.
SELECTBIO

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,900+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,200+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!