Parkinson’s Researchers Identify Mechanism Involved in Memory Degeneration

Parkinson’s Researchers Identify Mechanism Involved in Memory Degeneration

The abnormal alpha-synuclein characteristic of Parkinson’s disease interacts with the prion protein PrP, initiating a series of events that culminate in neuronal degeneration and cognitive impairment, a European study found.

But a drug from the caffeine family prevented this interaction, reversing degeneration and Parkinson’s symptoms in mice.

The study, “α-synuclein interacts with PrPC to induce cognitive impairment through mGluR5 and NMDAR2B,” appeared in the journal Nature Neuroscience.

Tiago Outeiro, director of the department of NeuroDegeneration and Restorative Research at Germany’s University Medical Center Göttingen, led the study along with researchers at Portugal’s Instituto de Medicina Molecular (iMM Lisboa) and Germany’s Max Planck Institute for Experimental Medicine.

Outeiro and his team had found that some forms of alpha-synuclein regulated neuronal circuits were associated with memory formation — but they didn’t know why.

Teaming up with Luisa Lopes, a principal investigator at iMM Lisboa, Outeiro revealed how alpha-synuclein is involved in memory degeneration in Parkinson’s.

“We did not know how this was happening, and in this new study we have detailed the molecular mechanisms involved, which suggests we now have new targets for therapeutic intervention,” Outeiro explained in a press release.

Added iMM Lisboa’s Lopes: “We are very excited with the findings of our collaboration, and this study demonstrates that when we pull together our complementary expertise we can make important discoveries that can impact the lives of the millions of people affected by these terrible disorders.”

The team found that physical interaction between alpha-synuclein and PrP triggered a cascade of signals that hampers communication among brain cells.

Using Parkinson’s mice models engineered to lack the PrP protein, the team found that the interaction between both proteins was essential in mediating the disease’s cognitive impairment characteristic. Importantly, they found that a molecule similar to caffeine was able to prevent this interaction, restoring memory deficits in mice.

“We used a mouse model of PD in which human alpha-synuclein is produced and found that blocking this interaction with PrP using a caffeine analogue reverted the abnormal neuronal activity and memory deficits,” Lopes said, explaining that “molecules like caffeine may indeed have potential benefits against memory deficits upon neurodegeneration.”

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