Parkinson’s disease (PD) is typically considered a condition of aging, characterized by the gradual loss of dopamine-producing neurons in the midbrain. But emerging evidence suggests that the vulnerability of these neurons may be shaped decades earlier—possibly even before birth.

Alena’s project, “Born to Degenerate? Tracing the Developmental Origins of Parkinson’s Disease,” focuses on the protein alpha-synuclein, encoded by the SNCA gene. Alpha-synuclein is best known for forming the toxic aggregates that are a hallmark of Parkinson’s disease. Yet its normal biological function remains poorly understood.

“Alpha-synuclein is strongly expressed in the embryonic brain, particularly in immature dopamine neurons—the very cells that later degenerate in Parkinson’s,” explains Alena. “This raises an intriguing possibility: that dysfunction of this protein during development could program neurons for future vulnerability.”

Previous studies have shown that mice lacking alpha-synuclein have fewer immature dopamine neurons, suggesting that the protein plays an important role during brain development. Alena’s project will build on this finding by investigating how alpha-synuclein influences the specification, maturation, and connectivity of these neurons—and whether early disruptions leave them more susceptible to stress and aging later in life.

Using advanced techniques such as light-sheet microscopy, tissue clearing, RNA sequencing, and proteomics, the project will map alpha-synuclein expression across developmental stages and create detailed 3D reconstructions of embryonic dopamine neuron networks. These approaches will help identify the molecular pathways controlled by alpha-synuclein and reveal mechanisms that contribute to long-term neuronal resilience or vulnerability.

By linking prenatal molecular events to the selective neuronal loss seen in Parkinson’s disease, this research challenges traditional views of PD as purely an age-related disorder.

“If our hypothesis is correct, Parkinson’s may need to be redefined as a condition with developmental origins,” says Alena. “That would open entirely new possibilities for early diagnosis, prevention, and neuroprotective therapies.”

The project represents an important step toward understanding why certain neurons are so vulnerable in Parkinson’s disease—and how that vulnerability might be prevented long before symptoms appear.

DANDRITE congratulates Alena on this exciting grant and looks forward to following the progress of this innovative research.

About the grant

• The Lundbeck Foundation awards Experiment Grants to support researchers with bold and original ideas that challenge traditional assumptions. At the end of 2025, DKK 57 million was awarded to 26 scientists from Danish research institutions.
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