Recent research suggests that the toxic clumping of the alpha-synuclein protein in Parkinson’s disease could be linked to a calcium imbalance in neurons. The study, conducted on both mouse and human cells, found that clumping of alpha-synuclein can lead to calcium levels reaching harmful levels in neurons early in the development of Parkinson’s disease.
It was discovered that single molecules of alpha-synuclein can activate a calcium pump in the cell membrane, which helps to maintain healthy calcium levels. However, when alpha-synuclein starts to clump, this activation shifts to another calcium pump inside the cell, disrupting the balance of calcium levels – which may be a tipping point for the development and progression of Parkinson’s disease.
This breakthrough sheds light on the underlying mechanisms of Parkinson’s and may provide new avenues for diagnosing and treating the disease by addressing calcium balance. The study titled “Monomeric α-synuclein activates the plasma membrane calcium pump” was published in The EMBO Journal.
New Insights into the Role of Calcium Pumps in Parkinson’s Disease
Researchers at Aarhus University’s Danish Research Institute of Translational Neuroscience (DANDRITE) discovered that free single units of alpha-synuclein activate a calcium pump, called PCMA, in the cell membrane, preventing harmful calcium buildup that can cause damage to neurons.
This activation was found to be particularly important in the presynaptic area of neurons, which is responsible for transmitting signals in the brain’s neural network. Dr. Poul Nissen, the study’s senior author, explained that the interaction between alpha-synuclein and PCMA occurs at the synapse, suggesting the significance of alpha-synuclein in calcium excretion from neurons.
This novel function of [alpha-synuclein] is relevant to calcium homeostasis [balance] of neurons.
The study also revealed that alpha-synuclein activates the calcium pump PMCA in the presence of negatively charged fatty molecules, implying its importance in maintaining calcium homeostasis in neurons and specifically at presynaptic compartments.
Potential Implications for Diagnosis and Treatment
The study also suggests a link between abnormal calcium flow and the early formation of alpha-synuclein toxic clumps in neurons from Parkinson’s patients, providing insight into the potential diagnostic and treatment strategies aimed at addressing early calcium changes in neurodegenerative diseases such as Parkinson’s.
These findings open the door to potential diagnostic and treatment strategies aimed at addressing early calcium changes in Parkinson’s and other neurodegenerative diseases, according to the researchers. The study provides new insights into the development and progression of Parkinson’s disease and may pave the way for innovative diagnostic and therapeutic approaches.
