24 Feb 2026
A new study shows how disrupted packaging of the neurotransmitter dopamine in nerve cells triggers toxic processes—and how simple energy supply (ATP) can repair them.
Parkinson's disease gradually destroys dopamine-producing nerve cells in a specific area of the midbrain, causing tremors, stiffness, and movement disorders. Two key characteristics are the accumulation of the protein α-synuclein in Lewy bodies and the loss of nerve cells that produce the neurotransmitter dopamine. "Dopamine oxidizes into toxic substances and causes lasting damage to nerve cells if it is not properly packaged in small vesicles – but the cause of this disruption in dopamine packaging has been unclear until now," says Lena Burbulla, Professor of Metabolic Biochemistry at the LMU Faculty of Medicine and member of the SyNergy Cluster of Excellence. She is the lead author of a study recently published in the journal Science Advances.
Study Director Lena Burbulla | © BMC/LMU
The researchers transformed induced pluripotent stem cells (iPSCs) from a Parkinson's patient with a mutation in the DJ-1 gene and genetically modified iPSCs lacking the DJ-1 gene into nerve cells. “The lack of DJ-1 leads to energy problems that occur in many variants of Parkinson's disease,” explains Burbulla. Using high-precision protein analysis (proteomics), state-of-the-art imaging, and sensitive dopamine sensors, the research team discovered how dopamine is incorrectly “packaged” in the cells.
The protein VMAT2, which is responsible for the safe packaging of dopamine in vesicles, does not function properly in Parkinson's nerve cells: it absorbs too little dopamine – on the one hand because there is a lack of energy in the form of ATP (adenosine triphosphate), the universal energy carrier in cells, and on the other hand because too little VMAT2 is produced by the cell. As a result, dopamine ultimately oxidizes into toxins. Another crucial factor is the accumulation of misfolded α-synuclein protein – probably a consequence of oxidized dopamine, which can bind proteins and promote their accumulation. As the researchers were able to show, a simple ATP infusion repaired the packaging of dopamine and stopped the damage.
Therapeutic potential of dopamine packaging
“This discovery links energy deficiency to dopamine packaging and nerve cell vulnerability—a new mechanism for Parkinson's disease,” says Burbulla. It shows that intact VMAT2 and secure dopamine packaging are key protective factors for midbrain nerve cells and that preserving them could slow down the pathology. “iPSC-based disease modeling enables future therapy testing directly in patient cells and accelerates translation from the laboratory to the clinic.”
Leonie Heger et al.: VMAT2 dysfunction impairs vesicular dopamine uptake, driving its oxidation and α-synuclein pathology in DJ-1–linked Parkinson’s neurons. Science Advances 2026