What you would see is a network of nerve cells called neurons, each with its own internal highway system for transporting essential materials between different parts of the cell.
When this biological machinery is operating smoothly, tiny motor proteins ferry precious cargo up and down each neuron along thread-like roadways called microtubule tracks. Brain cells are able to receive information, make internal repairs and send instructions to the body, telling the fingers to flex or the toes to curl.
But when the neuron gets blocked, this delicate harmony deteriorates. One result: diseases like Alzheimer’s.
Understanding such blockages and how traffic should flow normally in healthy brain cells could offer hope to people with neurodegenerative diseases.
Toward that end, a research team led by University at Buffalo biologist Shermali Gunawardena, PhD, has shown that the protein presenilin plays an important role in controlling neuronal traffic on microtubule highways, a novel function that previously was unknown.
The research results were published online on May 24 in the journal Human Molecular Genetics (http://bit.ly/ZqxSJ5). Gunawardena’s co-authors are Ge Yang of Carnegie Mellon University and Lawrence S. B. Goldstein of the Howard Hughes Medical Institute and the University of California, San Diego.
Inside the nerves of fruit fly larvae, presenilin helped to control the speed at which molecular motors called kinesins and dyneins moved along neurons. When the scientists halved the amount of presenilin present in the highway system, the motors moved faster; they paused fewer times and their pauses were shorter.
Given this data, Gunawardena thinks that tweaking presenilin levels may be one way to free up traffic and prevent dangerous neuronal blockages in patients with Alzheimer’s disease.
“Our major discovery is that presenilin has a novel role, which is to control the movement of motor proteins along neuronal highways,” said Gunawardena, an assistant professor of biological sciences. “If this regulation/control is lost, then things can go wrong. This is the first time a protein that functions as a controller of motors has been reported.
“In Alzheimer’s disease, transport defects occur well before symptoms, such as cell death and amyloid plaques, are seen in post-mortem brains,” she added. “As a result, developing therapeutics targeted to defects in neuronal transport would be a useful way to attack the problem early.”
The findings are particularly intriguing because scientists have known for several years that presenilin is involved in Alzheimer’s disease.
Presenilin rides along neuronal highways in tiny organic bubbles called vesicles that sit atop the kinesin and dynein motors, and also contain a second protein called the amyloid precursor protein (APP). Presenilin participates in cutting APP into pieces called amyloid beta, which build up to form amyloid plaques in patients with Alzheimer's disease.
Such buildups can lead to cell death by preventing the transport of essential materials—like proteins needed for cell repair—along neurons.
The findings of the new study mean that presenilin may contribute to Alzheimer’s disease in at least two ways: not just by cleaving APP, but also by regulating the speed of the molecular motors that carry APP along neuronal highways.
“More than 150 mutations in presenilin have been identified in Alzheimer’s disease,” Gunawardena said. “Thus, understanding its function is important to understanding what goes wrong in Alzheimer’s disease.”
To track the movement of the kinesins and dyneins, the team tagged their cargo with a yellow fluorescent protein. This enabled the scientists to view the molecular motors chugging along inside the neuron under a microscope in a living animal. A special computer program then analyzed the motors’ paths, revealing more details about the nature of their movement and how often they paused.Media Contact Information
Charlotte Hsu | EurekAlert!
Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory
Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine