Parkinson’s disease is a progressive neurological disorder that affects movement in the body. With a study published in Nature Medicine indicating that more than 57 million people across the globe suffer from neurodegenerative disease, a figure expected to double every 20 years as the population ages, it is imperative to further our understanding of the causes of Parkinson’s disease, as well as the conflicting side effects of a therapeutic drug used to alleviate its symptoms.
The capability of mass spectrometry imaging (MSI) to detect a range of neuroactive compounds and metabolites in a single tissue section has firmly established its potential in neuroscientific research. This article will explore the ground-breaking research by the Spatial Mass Spectrometry group at Uppsala University in Sweden, one of the largest centres for life sciences in Europe, into Parkinson’s disease, specifically a specific stage of the disease, called levodopa (L-DOPA)induced dyskinesia (LID), which develops in approximately 50 percent of patients after five to six years of L-DOPA treatment.
A Deeper Understanding of Parkinson’s Disease
Parkinson’s disease is an incurable neurodegenerative disease caused by the loss of dopamine-producing nerve cells in the brain. It is characterised by motor dysfunction, tremors, bradykinesia (or slowed movement), muscle rigidity, and postural instability including involuntary and unpredictable body movements.
L-3,4-dihydroxyphenylalanine (levodopa, or L-DOPA) administration is the primary treatment for Parkinson’s. L-DOPA is a precursor to dopamine that crosses the blood-brain barrier where it is converted into dopamine, replenishing the brain’s depleted supply of dopaminergic neurons in the substantia nigra pars compacta region that leads to reduced dopamine in the striatum, an area of the brain responsible for movement control in the body.
L-DOPA is highly effective in the early stages, but its long-term use is often accompanied by the side-effect LID, a treatment-limiting complication which exhibits as involuntary, erratic, and uncontrollable tremors and whose pathophysiology is poorly understood.
LID has a significant negative impact on quality of life. What is not yet known is why only certain people are affected. Working with animal models, as well as human bloodcerebrospinal fluid (CSF) biobank samples supplied by collaborators at the Karolinska Institute, Stockholm, Bordeaux University, and Kings College London, researchers in the Department of Pharmaceutical Biosciences at Uppsala University are using MSI to investigate the elevated L-DOPA levels in the brain that are linked with LID.
