Nav: Home

New therapeutic strategy to treat Alzheimer's

February 20, 2019

Researchers from the Institute of Neurosciences of the University of Barcelona (UBNeuro) have identified a potential therapeutic strategy to treat Alzheimer's, according to a study published in Journal of Neuroscience. The study shows, in a model of the illness in mice, that astrocytes -a type of cells in the brain- are able to release proteins that favour survival of neurons. According to the researchers, these results are a step forward in the understanding of the physiology of astrocytes, and they bring the chance to use this type of cells in therapeutic ways to treat Alzheimer's.

The study is led by Albert Giralt, Ramon y Cajal researcher at the UB, and also signed by the experts Jordi Alberch, Laura López Molina, Anna Sancho-Balsells, Ana López and Silvia Ginés, from the Faculty of Medicine and Health Sciences and UBNeuro, and members of the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) and the Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED).

Other participants in the study are José María Delgado García and Angès Gruart, from Universidad Pablo de Olavide, and other experts from Inserm (France) and Institut du Fer à Moulin (France).

A promising strategy with important challenges

Alzheimer's disease is the most common dementia among people. Neurodegeneration in patients with this disease causes damage in memory and in other cognitive skills, sometimes combined with symptoms such as mood swings and personality changes. One of the most promising therapies against Alzheimer's is the use of neurotrophic factors -a family of proteins favouring neuron survival- such as the brain-derived neurotrophic factor (BDNF). However, BDNF administration has important challenges, such as the lack of control of its release, which does not allow leading it specifically to the sick tissue nor releasing the proper amount of levels, mainly considering high doses can be neurotoxic.

In this study, researchers studied BDNF generated by astrocytes, a type of star-shaped glial cells in the brain and the spinal cord. Astrocytes are affected by one of the neuroinflammation processes of Alzheimer's, the astrogliosis, in which the glial fibrillary astrocytic protein (GFAP) and its coding gene are the most altered ones. In this context, researchers designed an experiment in which genetically modified mice suffer from Alzheimer's and produce the BDNF protein depending on the GFAP levels. "With this design, from the moment neuroinflammation and pathology came up, the astrocytes could generate BDNF in the most affected areas of the sick brain. Therefore, the endogen reactions of the brain would regulate BDNF administration depending on the severity of the disease", says Albert Giralt, member of the Consolidated Research Group on Physiopathology of Neurodegenerative Diseases of the UB.

Effects of neuron formation and plasticity

The study shows this method restores the production and release of the neurotrophin in the sick neuronal tissue when the pathology starts. Then, the BDNF generated by astrocytes regulates neuron formation in samples of in vitro neuronal cultures and has cognitive effects in transgenic mice models. "These results show for the first time that astrocytes, so far regarded as neuronal, can produce BDNF and have the necessary molecular mechanisms to release it in the areas of the diseased tissue which requires activity to favour neuronal survival", says Albert Giralt.

Researchers also note that "the singularity of the design of the experiment enabled the astroglial cells to 'decide' when, where and what amount to produce and give BDNF to altered brain tissues". Therefore, "traits of the patient can mark endogenously and self-regulated the dose and other necessary therapeutic dynamics for a customized treatment".

Although the use of this therapy in humans is still far from taking place, researchers note the use of astrocytes out of induced pluripotent stem cells as a promising therapeutic strategy to be explored. "One possibility would be to derive induced stem cells from the skin of the patients, and then modify them genetically in vitro to express the BDNF under the GFAP promoter. Last, the last step would be to differentiate them and move them to the most altered brain regions of patients to boost survival and proper functioning of the existing neurons", notes Albert Giralt.

Viability in other neurodegenerative diseases

This study using neuroinflammation processes makes it possible to apply them to other neurodegenerative diseases. "Our objective is, on the one hand, making this therapeutic approach plausible for the use in humans, and on the other, present similar approaches for neurodegenerative diseases in which neuroinflammation is a main symptom", concludes the researcher.
-end-


University of Barcelona

Related Neurons Articles:

New tool to identify and control neurons
One of the big challenges in the Neuroscience field is to understand how connections and communications trigger our behavior.
Neurons that regenerate, neurons that die
In a new study published in Neuron, investigators report on a transcription factor that they have found that can help certain neurons regenerate, while simultaneously killing others.
How neurons use crowdsourcing to make decisions
When many individual neurons collect data, how do they reach a unanimous decision?
Neurons can learn temporal patterns
Individual neurons can learn not only single responses to a particular signal, but also a series of reactions at precisely timed intervals.
A turbo engine for tracing neurons
Putting a turbo engine into an old car gives it an entirely new life -- suddenly it can go further, faster.
Brain neurons help keep track of time
Turning the theory of how the human brain perceives time on its head, a novel analysis in mice reveals that dopamine neuron activity plays a key role in judgment of time, slowing down the internal clock.
During infancy, neurons are still finding their places
Researchers have identified a large population of previously unrecognized young neurons that migrate in the human brain during the first few months of life, contributing to the expansion of the frontal lobe, a region important for social behavior and executive function.
How many types of neurons are there in the brain?
For decades, scientists have struggled to develop a comprehensive census of cell types in the brain.
Molecular body guards for neurons
In the brain, patterns of neural activity are perfectly balanced.
Engineering researchers use laser to 'weld' neurons
University of Alberta researchers have developed a method of connecting neurons, using ultrashort laser pulses -- a breakthrough technique that opens the door to new medical research and treatment opportunities.

Related Neurons Reading:

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

Jumpstarting Creativity
Our greatest breakthroughs and triumphs have one thing in common: creativity. But how do you ignite it? And how do you rekindle it? This hour, TED speakers explore ideas on jumpstarting creativity. Guests include economist Tim Harford, producer Helen Marriage, artificial intelligence researcher Steve Engels, and behavioral scientist Marily Oppezzo.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".