Researchers have found that neurons can burn and even make their own fat to power the brain. A faulty protein stops this process in people with a rare brain disease, leaving neurons weak and damaged.
By feeding the cells certain fats, scientists were able to restore their energy and function in just 48 hours. The discovery could lead to new ways to heal the brain and reverse neurological damage.
How a Faulty Protein Disrupts Brain Energy
Researchers from the University of Queensland (Australia) and the University of Helsinki (Finland) have uncovered evidence that neurons can use fat as a source of energy, challenging the long-held belief that they rely only on sugar. Even more intriguing, neurons can produce their own fats when they need extra fuel by recycling parts of their own cells. This process depends on a crucial protein known as DDHD2.
A rare neurological condition called Hereditary Spastic Paraplegia 54 (HSP54) occurs when the DDHD2 protein does not function as it should. Without this protein, neurons lose the ability to create the fats they need for energy and normal communication, which leads to early and progressively worsening problems with sending signals.
Children with HSP54 often begin experiencing difficulties with movement and thinking at an early age. However, the new findings offer renewed hope. In laboratory studies, scientists gave damaged neurons specific fatty acid supplements and found that within only 48 hours the cells regained their energy and began functioning more normally.
“This is a real game-changer,” said Dr. Merja Joensuu, who conceived the project and led the study at the Australian Institute for Bioengineering and Nanotechnology. “We’ve shown that healthy neurons rely on fats for fuel, and when this pathway fails in conditions like HSP54, it may be possible to repair the damage and reverse the neuropathologies.”
Moving Toward Future Treatments
The next step for the team is to evaluate whether these fatty acid-based treatments are safe and effective in pre-clinical models. This work will help determine whether similar therapies could eventually be tested in humans and whether this fat-based energy pathway may be useful for treating other brain disorders that currently have no available therapies.
“We will continue the exciting collaboration with new non-invasive technologies to image the brain and therefore aid the faster development of the potential therapy. This breakthrough doesn’t just rewrite the textbooks, it could transform lives,” Dr. Giuseppe Balistreri from the University of Helsinki says.
Reference: “DDHD2 provides a flux of saturated fatty acids for neuronal energy and function” by Saber H. Saber, Nyakuoy Yak, Xuan Ling Hilary Yong, Yih Tyng Bong, Hannah Leeson, Chuan-Yang Dai, Tobias Binder, Siyuan Lu, Reshinthine Purushothaman, An-Sofie Lenaerts, Leonardo Almeida-Souza, Lidiia Koludarova, Safak Er, Irena Hlushchuk, Arnaud Gaudin, Sachin Singh, Tuula A. Nyman, Jeffrey R. Harmer, Steven Zuryn, Ernst Wolvetang, Gert Hoy Talbo, Mikko Airavaara, Brendan J. Battersby, Ashley J. van Waardenberg, Victor Anggono, Giuseppe Balistreri and Merja Joensuu, 30 September 2025, Nature Metabolism.
DOI: 10.1038/s42255-025-01367-x
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