Our skin cells could tell a tale of Parkinson’s without us even knowing

Parkinson’s disease is chronic disease that normally affects older individuals. Once the symptoms such as tremors or gait difficulties are first observed, significant neuronal damage has already occurred, resulting in progressive brain deterioration.

But what if it was possible to detect Parkinson’s disease, before development of severe damage? It looks like this might not be a remote possibility as currently thought, and the method to achieve this important goal could even be relatively simple and cheap.

“It turns out that Parkinson’s disease might be detected in our skin cells. At least in patients affected by a common form of the disease that is genetically inherited. In our study, we can see that specific lipids are significantly changed in the skin of these patients. And our dream scenario would be if this would also be the case years before the disease develops,” says author to the study Céline Galvagnion-Büll, Associate Professor at the Department of Drug Design and Pharmacology.

First detection in the skin

In the study, the researchers investigated skin from 5 patients with familial Parkinson’s disease, 4 patients with so-called sporadic Parkinson’s and 4 healthy controls.

They could see a significant change of the lipids in the skin cells, called fibroblasts, from the patients with familial Parkinson’s.

“We wanted to investigate this because we know that patients with this familial form of Parkinson’s have genetic mutations that causes an enzyme to malfunction in our cells. We thought that this malfunctioning enzyme could affect the molecular makeup of the lipids in the skin. This is the first time that anyone has been able to link changes in skin lipid makeup to disease state,” says Céline Galvagnion-Büll.

The lipids are made of two parts: the head that is hydrophilic (“water-loving”) and the chains that are hydrophobic (“water-fearing”). In the new study, the researchers were able to measure the length of these chains in order to investigate the lipid composition of the skin cells.

Drug can revert lipids back to normal

“The changes that we see in the lipids in skin cells may occur in all cells when you have the genetic mutation, including brain cells,” says Céline Galvagnion-Büll.

Another important component of the study concerns interactions between lipids and alpha-synuclein. In Parkinson’s disease, the protein alpha synuclein accumulates into toxic clumps in the brain. It is quite likely that these alpha-synuclein deposits contribute to neuronal injury and disease progression. For this reason, great research efforts have been made over the past years and are currently continuing in order to identify mechanisms that cause the accumulation of these toxic clumps form and to design therapeutic strategies to avoid it. The new research also gives a new perspective on this matter.

“Our new research results indicate that the changed lipids actually make the protein clump together faster. This might prove to be tremendously important knowledge,” explains Céline Galvagnion-Büll.

The researchers also tested whether a small molecule drug, currently in clinical trial against both familial and sporadic Parkinson’s disease, could affect the cellular lipid makeup and the formation of alpha-synuclein clumps.

“The drug actually reverted the changes of the lipids in the skin back to normal. That is encouraging for us to see. If this is also the case for brain cells, then this could potentially be an effective strategy to counteract Parkinson’s disease progression,” she says.

Now, the researchers will try to use stem cells to develop neurons and test whether the same is true for brain cells.

This work involved scientists from the German Center for Neurodegenerative Disease (DZNE) in Bonn the University College London and the IRCCS Mondino Foundation in Pavia.

The new results are published in the scientific journal Brain: “Sphingolipid changes in Parkinson L444P GBA mutation fibroblasts promote α-synuclein aggregation”

Contact

Associate Professor Céline Galvagnion-Büll
Department of Drug Design and Pharmacology
+45 35 33 78 28
celine.galvagnion@sund.ku.dk

Press Officer Mathias Traczyk
93 56 58 35
mathias.traczyk@sund.ku.dk