The specific subset of brain cells that die off in patients with Parkinson’s disease has been identified, thus solving one of the greatest mysteries surrounding the disorder. Presenting their research in the journal Nature Neuroscience, the study authors say their findings could lead to the development of new treatments that target these vulnerable neurons.
The degradation of dopamine neurons within a brain region called the substantia nigra pars compacta (SNpc) is a major hallmark of Parkinson’s disease and other forms of dementia. Because dopamine helps regulate mood, cognition, and motor control, the loss of these cells often leads to symptoms including tremors, depression, and cognitive decline.
However, not all of the dopamine neurons in the SNpc are affected, with some dying off in the early stages of the disease while others remain intact. To understand why this is the case, the study authors looked at a total of 22,048 brain cells from 10 deceased Parkinson’s and dementia patients and eight people who died without any cognitive disorders.
After measuring patterns of gene expression within these cells, they found that there are in fact 10 distinct subpopulations of dopamine neurons within the SNcp, distinguishable by their unique transcriptional profile. One of these groups was predominantly localized on the ventral region – or underside – of the SNcp, which matches previously identified patterns of neuronal degeneration in dementia.
Sure enough, when the researchers looked at the brains of their late study participants, they found that this group of neurons was largely missing from the Parkinson’s and dementia sufferers. A more detailed analysis of these cells revealed an upregulation of genes that are strongly implicated in cell death processes, suggesting that these neurons may be the first to become damaged in individuals with neurodegenerative conditions.
The smoking gun was then confirmed when the authors noted that this particular subset of neurons contained the highest expression of genes associated with the risk of developing Parkinson’s disease. Taken together, these observations appear to indicate that this group of neurons is particularly vulnerable to degeneration in people with a genetic susceptibility to the illness, and that the loss of these cells may be predominantly responsible for many of the symptoms associated with the condition.
The study authors, therefore, call for future research to focus specifically on this subpopulation of cells, suggesting that they may hold the key to treating Parkinson’s disease.
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