Nav: Home

The connection between excess iron and Parkinson's disease

January 26, 2016

It's long been known that excess iron is found in the brains of patients with Parkinson's disease (PD), an incurable neurodegenerative condition that affects motor function. The mechanism by which the iron wreaks damage on neurons involved in PD has not been clear. Research from the Andersen lab at the Buck Institute suggests that the damage stems from an impairment in the lysosome, the organelle that acts as a cellular recycling center for damaged proteins. Scientists report the impairment allows excess iron to escape into the neurons where it causes toxic oxidative stress. The research will be published online in The Journal of Neuroscience on Jan. 27, 2016.

Lysosomes are key to a process called autophagy, whereby damaged proteins are broken down into building blocks that are used to make newly-built proteins to take their place. It's the cellular equivalent of recycling. With age, the ability of the lysosome to participate in autophagy becomes slower, resulting in the build-up of non-protein "garbage" within the cells. Less-than-optimal autophagy has been associated with several age-related diseases, including PD.

"It's recently been realized that one of the most important functions of the lysosome is to store iron in a place in the cell where it is not accessible to participate in toxic oxidative stress-producing reactions," said Julie K. Andersen, PhD, senior scientist and Buck Institute faculty. "Now we have demonstrated that a mutation in a lysosomal gene results in the toxic release of iron into the cell resulting in neuronal cell death."

Spearheaded by staff scientist Shankar J. Chinta, PhD, the work (done in both mice and cultured human dopaminergic cells) involved a mutation in a gene (ATP13A2) associated with a rare early onset form of PD called Kufor-Rakeb syndrome. When researchers knocked out ATP13A2 the lysosome was unable to maintain the balance of iron within the cell.

The mutation responsible for Kufor-Rakeb was identified in 2010. Those suffering from the condition, which is named for the village in Jordan where the syndrome was first described, experience disease onset in adolescence. "Mutations in this same gene have also been recently linked to sporadic forms of PD," said Andersen. "This suggests that age-related impairments in lysosomal function that impact the ability of neurons to maintain a healthy balance of iron are part of what underlies the presentation of PD in the general population."

Andersen has a long-standing interest in the role of excess iron in PD and this current work provides an example of the value of basic research in drug discovery. In 2003 her lab showed that tying up excess iron with a metal chelator (derived from the Greek word for claw) protected mice from the ravaging effects of the well-known Parkinson's inducing toxin, MPTP. The study provided an important link between the observed excessive iron in the brains of PD patients and oxidative stress associated with neurodegeneration. "The issue with iron chelation is that it's a sledge hammer -- it pulls iron from the cells indiscriminately and iron is needed throughout the body for many biological functions," said Andersen. "Now we have a more specific target that we can hit with a smaller hammer, which could allow us to selectively impact iron toxicity within the affected neurons."
-end-
Citation: "Regulation of ATP13A2 via PHD2-HIF1a Signaling is Critical for Cellular Iron Homeostasis: Implications for Parkinson's Disease" DOI: 10.1523/JNEUROSCI.3117-15.2016

Other Buck scientists involved in the study include Subramanian Rajagopalan and Anand Rane. This work was supported by the National Institutes of Health (RO1 NS047198, NS047198, NS041264, and AG012141).

About the Buck Institute for Research on Aging

The Buck Institute is the U.S.'s first independent research organization devoted to Geroscience -- focused on the connection between normal aging and chronic disease. Based in Novato, CA, The Buck is dedicated to extending "Healthspan", the healthy years of human life and does so utilizing a unique interdisciplinary approach involving laboratories studying the mechanisms of aging and those focused on specific diseases. Buck scientists strive to discover new ways of detecting, preventing and treating age-related diseases such as Alzheimer's and Parkinson's, cancer, cardiovascular disease, macular degeneration, osteoporosis, diabetes and stroke. In their collaborative research, they are supported by the most recent developments in genomics, proteomics, bioinformatics and stem cell technologies. For more information: http://www.thebuck.org

Buck Institute for Research on Aging

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)

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

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

From Neuron to Brain: A Cellular and Molecular Approach to the Function of the Nervous System, Fourth Edition
by John G. Nicholls (Author), A. Robert Martin (Author), Bruce G. Wallace (Author), Paul A. Fuchs (Author)

From Photon to Neuron: Light, Imaging, Vision
by Philip Nelson (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)

From Neurons to Neighborhoods: An Update: Workshop Summary
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)

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

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 7 Secrets of Neuron Leadership: What Top Military Commanders, Neuroscientists, and the Ancient Greeks Teach Us about Inspiring Teams
by W. Craig Reed (Author), Gordon R. England (Foreword)

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Hacking The Law
We have a vision of justice as blind, impartial, and fair — but in reality, the law often fails those who need it most. This hour, TED speakers explore radical ways to change the legal system. Guests include lawyer and social justice advocate Robin Steinberg, animal rights lawyer Steven Wise, political activist Brett Hennig, and lawyer and social entrepreneur Vivek Maru.
Now Playing: Science for the People

#495 Earth Science in Space
Some worlds are made of sand. Some are made of water. Some are even made of salt. In science fiction and fantasy, planet can be made of whatever you want. But what does that mean for how the planets themselves work? When in doubt, throw an asteroid at it. This is a live show recorded at the 2018 Dragon Con in Atlanta Georgia. Featuring Travor Valle, Mika McKinnon, David Moscato, Scott Harris, and moderated by our own Bethany Brookshire. Note: The sound isn't as good as we'd hoped but we love the guests and the conversation and we wanted to...