

The molecular interaction could reveal why some brain cells are more vulnerable than others in Parkinson’s disease.
Researchers at Imperial College London have uncovered a crucial clue to why some brain cells are more vulnerable to damage than others in Parkinson’s disease. The study published in Science Advances identifies a specific mitochondrial mechanism that could help explain why certain neurons deteriorate earlier in the disease, while others are largely unaffected.
Parkinson’s disease primarily affects neurons that produce dopamine, a chemical critical for movement and coordination. But among these dopamine-producing neurons, not all are equally at risk from damage.
The study focused on two key brain regions: the substantia nigra, where neurons are especially vulnerable to early damage, and a nearby area of the brain called the ventral tegmental, where neurons tend to remain more resilient.
The researchers investigated the interaction between DJ-1, a protein genetically linked to inherited forms of Parkinson’s, and the mitochondrial mechanisms in cells which are responsible for producing cellular energy. They found that in brains affected by Parkinson’s, this interaction was reduced in the neurons most vulnerable to degeneration.
According to the study’s senior author Dr Kambiz N. Alavian, Reader in Neuroscience from the Department of Brain Sciences, the answer may lie not in the amount of energy the mitochondria produce, but in how efficiently they produce in neurons:
“Neurons are some of the most energy-demanding cells in the body, and even a subtle reduction in mitochondrial efficiency can tip the balance from health to degeneration." Dr Kambiz N. Alavian
“Mitochondria aren’t simply tasked with making energy at all costs - they need to make energy as efficiently as possible, generating maximum output from minimal resources while minimising waste,” said Dr Alavian. “Neurons are some of the most energy-demanding cells in the body, and even a subtle reduction in mitochondrial efficiency - how well mitochondria utilise resources for energy production - can tip the balance from health to degeneration. What we’ve found is a molecular fingerprint of this inefficiency in the very neurons that regulate movement and die in Parkinson’s disease. Our findings give us a powerful new angle for understanding the disease.”
As the next step in their research, the scientists are now delving further into this mechanism to understand how it is regulated—and, more importantly, how it might be supported, restored, or eventually targeted with therapeutics. By breaking down the molecular steps that maintain mitochondrial efficiency, they aim to identify specific factors that can be modulated to strengthen cellular energy systems and protect vulnerable neurons.
“There’s exciting potential here,” Dr Alavian added. “Because mitochondrial efficiency can be influenced by factors such as diet, lifestyle, and nutraceutical and pharmaceutical interventions - and we already have evidence showing that this specific mechanism responds to such factors and interventions - this opens up new directions for how we might one day prevent or slow the progression of Parkinson’s disease.”
Article text (excluding photos or graphics) © Imperial College London.
Photos and graphics subject to third party copyright used with permission or © Imperial College London.
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Meesha Patel
Faculty of Medicine Centre

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