Nav: Home

Defective glial cells can push neurons toward Parkinson's disease

January 10, 2019

Researchers from the University of Barcelona have shown that defective versions of human brain cells called astrocytes are linked to the buildup of a toxic protein that is the hallmark of Parkinson's disease. The studied astrocytes, derived from Parkinson's disease patients with a genetic mutation that affects cell clean-up functions, caused more accumulation of the toxin, alpha-synuclein, than those derived from healthy individuals. The work, which appears January 10 in the journal Stem Cell Reports, suggests an important role for glial cells in Parkinson's disease and offers potential new targets for developing therapies.

"We have shown that astrocytes play a crucial role in Parkinson's disease. Our results demonstrate that Parkinson's disease astrocytes transfer a toxic protein to dopamine-producing neurons," says co-first author Angelique di Domenico, former postdoctoral fellow at the University of Barcelona's Bellvitge Biomedical Research Institute.

Star-shaped astrocytes extend branching tendrils around synapses and along blood vessels. One previous postmortem study found that Parkinson's patients had a buildup of alpha-synuclein--a protein that accumulates to form Lewy bodies, the signature pathology of Parkinson's disease--in their neurons as well as their astrocytes. It was this observation that led the researchers to examine astrocytes' role in the disease.

Using cells derived from Parkinson's patients with an LRRK2 mutation, the researchers generated stem-cell-derived glia cells. Fifteen percent of Parkinson's cases are tied to an inherited gene mutation, and 7 percent of all cases--inherited and sporadic--are linked to a large protein complex called LRRK2. LRRK2's main function is still unknown, but it seems to play a role in mitochondrial dynamics and autophagy, a process through which cells break down and rebuild their damaged components.

The researchers then used CRISPR gene editing to track the toxic alpha-synuclein as it was generated by the stem-cell-derived astrocytes and transferred to dopamine-producing neurons.

"We found Parkinson's disease astrocytes to have fragmented mitochondria, as well as several disrupted cellular degradation pathways, leading to the accumulation of alpha-synuclein," di Domenico says.

The accumulation of alpha-synuclein caused the targeted neurons' projecting branches--axons and dendrites--to shorten and disintegrate, resulting in neuronal death, she says.

In contrast, when healthy astrocytes were cultured with neurons from Parkinson's disease patients, axons and dendrites regenerated and alpha-synuclein was prevented from accumulating, ultimately restoring neuronal function, she notes.

The researchers used a drug--developed to treat abnormal intracellular buildup of toxic materials--on the Parkinson's disease astrocytes. "We were elated to see after treatment that the cellular degradation processes were restored and alpha-synuclein was completely cleared from the Parkinson's disease astrocytes," di Domenico says. "These results pave the way to new therapeutic strategies that block pathogenic interactions between neurons and glial cells."

Next steps involve investigating astrocytes from the 85 to 90 percent of Parkinson's cases that are sporadic, with no known genetic cause.
-end-
This work was supported by the European Research Council-ERC, the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III, AGAUR, and CERCA Programme / Generalitat de Catalunya.

Stem Cell Reports, di Domenico et al.: "Patient-specific iPSC-derived astrocytes contribute to non-cell autonomous neurodegeneration in Parkinson's disease" https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(18)30530-7

Stem Cell Reports, published by Cell Press for the International Society for Stem Cell Research (@ISSCR), is a monthly open-access forum communicating basic discoveries in stem cell research, in addition to translational and clinical studies. The journal focuses on shorter, single-point manuscripts that report original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. Visit http://www.cell.com/stem-cell-reports. To receive Cell Press media alerts, please contact press@cell.com.

Cell Press

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:

The Neuron: Cell and Molecular Biology
by Irwin B. Levitan (Author), Leonard K. Kaczmarek (Author)

Mirror Neurons Will Save Your Life: How To Stop Being Controlled By Other People

From Neuron to Brain (5th Ed)
by John G. Nicholls (Author), A. Robert Martin (Author), David A. Brown (Author), Mathew E. Diamond (Author), David A. Weisblat (Author), Paul A. Fuchs (Author)

The Neuron: Cell and Molecular Biology
by Irwin B. Levitan (Author), Leonard K. Kaczmarek (Author)

From Neurons to Neighborhoods : The Science of Early Childhood Development
by Committee on Integrating the Science of Early Childhood Development (Author), Youth, and Families Board on Children (Author), National Research Council (Author), Committee on Integrating the Science of Early Childhood Development (Author), Jack P. Shonkoff (Editor), Deborah A. Phillips (Editor)

Neurons in Action 2: Tutorials and Simulations using NEURON
by John W. Moore (Author), Ann E. Stuart (Author)

From Neurons to Neighborhoods: An Update: Workshop Summary (BCYF 25th Anniversary)
by National Research Council (Author), Division of Behavioral and Social Sciences and Education (Author), Institute of Medicine (Author), Youth, and Families Board on Children (Author), Steve Olson (Editor)

Did My Neurons Make Me Do It?: Philosophical and Neurobiological Perspectives on Moral Responsibility and Free Will
by Nancey Murphy (Author), Warren S. Brown (Author)

The Myth of Mirror Neurons: The Real Neuroscience of Communication and Cognition
by W. W. Norton & Company

I of the Vortex: From Neurons to Self
by Rodolfo R. Llinas (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.