Nav: Home

Researchers answer decades-old question about protein found in Alzheimer's brain plaques

January 10, 2019

Alzheimer's-affected brains are riddled with so-called amyloid plaques: protein aggregates consisting mainly of amyloid-β. However, this amyloid-β is a fragment produced from a precursor protein whose normal function has remained enigmatic for decades. A team of scientists at VIB and KU Leuven led by professors Joris de Wit and Bart De Strooper has now uncovered that this amyloid precursor protein modulates neuronal signal transmission through binding to a specific receptor. Modulating this receptor could potentially help treat Alzheimer's or other brain diseases. The results are published in Science.

More than 30 years have passed since the amyloid precursor protein was first identified. In the late 1980s, several research teams across the globe traced the protein fragment found in amyloid plaques back to a gene located on chromosome 21. The gene encodes a longer protein that is cleaved into several fragments, one of which ends up in amyloid plaques.

Decades of research have focused on the cleavage process that leads to the formation of the amyloid-β fragment and its subsequent aggregation, in the hope of identifying new therapeutic avenues for Alzheimer's. Meanwhile, an important question remained unanswered: what does the rest of the amyloid precursor protein actually do?

In search of a binding partner

To answer this question, Dr. Heather Rice, a postdoctoral researcher in the labs of Joris de Wit and Bart De Strooper at the VIB-KU Leuven Center for Brain & Disease Research, set out to identify the nerve cell receptor that interacts with the amyloid precursor protein.

"We knew that the amyloid precursor protein exerts its role through the part of the protein that is released outside of the cell. To understand its function, we needed to look for binding partners located on the cell surface," explains Rice.

The researchers identified a receptor present at the synapse, the structure where two different neurons connect to pass on signals. "We found that the secreted part of the amyloid precursor protein interacts with a receptor called GABABR1a, and that this in turn suppressed neuronal communication at the synapse," says Rice.

Modulating signal transmission

"Although mutations in the amyloid precursor protein in familial cases of Alzheimer's disease all affect the production of amyloid-β, we don't really know whether other aspects of the protein's function contribute to Alzheimer's as well," says Bart De Strooper. He believes that the new findings add a fresh perspective to previous studies on the amyloid precursor protein and Alzheimer's disease. "The newly identified role of the amyloid precursor protein may underlie the neuronal network abnormalities we see in mouse models of Alzheimer's disease and preceding clinical onset in human patients. It is exciting to consider that a therapy targeting this receptor might attenuate these abnormalities in people with Alzheimer's."

De Wit adds that the clinical implications may reach much further than just Alzheimer's: "Interestingly, GABABR signaling has been implicated in a diverse range of neurological and psychiatric disorders, including epilepsy, depression, addiction and schizophrenia. Now that we know how the secreted part of the amyloid precursor protein modulates neuronal signaling through the GABAB receptor, we could think of new ways to develop drugs that can restore this type of neuronal signaling in other clinical contexts."
-end-
Publication

Secreted amyloid-β precursor protein functions as a GABABR1a ligand to modulate synaptic transmission, Rice et al., Science 2019

Questions from patients

A breakthrough in research is not the same as a breakthrough in medicine. The realizations of VIB researchers can form the basis of new therapies, but the development path still takes years. This can raise a lot of questions. That is why we ask you to please refer questions in your report or article to the email address that VIB makes available for this purpose: patienteninfo@vib.be. Everyone can submit questions concerning this and other medically-oriented research directly to VIB via this address.

VIB (the Flanders Institute for Biotechnology)

Related Protein Articles:

Hi-res view of protein complex shows how it breaks up protein tangles
A new, high-resolution view of the structure of Hsp104 (heat shock protein 104), a natural yeast protein nanomachine with six subunits, may show news ways to dismantle harmful protein clumps in disease.
Breaking the protein-DNA bond
A new Northwestern University study finds that unbound proteins in a cell break up protein-DNA bonds as they compete for the single-binding site.
FASEB Science Research Conference: Protein Kinases and Protein Phosphorylation
This conference focuses on the biology of protein kinases and phosphorylation signaling.
Largest resource of human protein-protein interactions can help interpret genomic data
An international research team has developed the largest database of protein-to-protein interaction networks, a resource that can illuminate how numerous disease-associated genes contribute to disease development and progression.
STAT2: Much more than an antiviral protein
A protein known for guarding against viral infections leads a double life, new research shows, and can interfere with cell growth and the defense against parasites.
A protein makes the difference
It is well-established knowledge that blood vessels foster the growth of tumors.
Nuclear protein causes neuroblastoma to become more aggressive
Aggressive forms of neuroblastoma contain a specific protein in their cells' nuclei that is not found in the nuclei of more benign forms of the cancer, and the discovery, made through research from the University of Rochester Medical Center, could lead to new forms of targeted therapy.
How a protein could become the next big sweetener
High-fructose corn syrup and sugar are on the outs with calorie-wary consumers.
High animal protein intake associated with higher, plant protein with lower mortality rate
The largest study to examine the effects of different sources of dietary protein found that a high intake of proteins from animal sources -- particularly processed and unprocessed red meats -- was associated with a higher mortality rate, while a high intake of protein from plant sources was associated with a lower risk of death.
Protein in, ammonia out
A recent study has compiled and analyzed data from 25 previous studies.

Related Protein Reading:

Proteins: Structure and Function
by David Whitford (Author)

Proteins: Concepts in Biochemistry
by Paulo Almeida (Author)

The Effective Vegan Diet: 50 High Protein Recipes for a Healthier Lifestyle

Protein Power: The High-Protein/Low Carbohydrate Way to Lose Weight, Feel Fit, and Boost Your Health-in Just Weeks!
by Michael R. Eades (Author), Mary Dan Eades (Author)

DIY Protein Bars Cookbook [3rd Edition]: Easy, Healthy, Homemade No-Bake Treats That Are Packed With Protein!
by Jessica Stier (Author)

The High-Protein Vegetarian Cookbook: Hearty Dishes that Even Carnivores Will Love
by Katie Parker (Author), Kristen Smith (Author)

Janeva's Ideal Recipes: A Personal Recipe Collection for the Ideal Protein Phase 1 Diet [Revised Version 1]
by Janeva Caroline Eickhoff (Author)

The High-Protein Vegan Cookbook: 125+ Hearty Plant-Based Recipes
by Ginny Kay McMeans (Author)

The High-Protein Cookbook: More than 150 healthy and irresistibly good low-carb dishes that can be on the table in thirty minutes or less.
by Linda West Eckhardt (Author), Katherine West Defoyd (Author)

Protein Sparing Modified Fast Cookbook
by Maria Emmerich (Author), Craig Emmerich (Author)

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Approaching With Kindness
We often forget to say the words "thank you." But can those two words change how you — and those around you — look at the world? This hour, TED speakers on the power of gratitude and appreciation. Guests include author AJ Jacobs, author and former baseball player Mike Robbins, Dr. Laura Trice, Professor of Management Christine Porath, and former Danish politician Özlem Cekic.
Now Playing: Science for the People

#509 Anisogamy: The Beginning of Male and Female
This week we discuss how the sperm and egg came to be, and how a difference of reproductive interest has led to sexual conflict in bed bugs. We'll be speaking with Dr. Geoff Parker, an evolutionary biologist credited with developing a theory to explain the evolution of two sexes, about anisogamy, sexual reproduction through the fusion of two different gametes: the egg and the sperm. Then we'll speak with Dr. Roberto Pereira, research scientist in urban entomology at the University of Florida, about traumatic insemination in bed bugs.