What are the causes of Parkinson's memory gaps?

Researchers discovered mechanism leading to memory deficits in Parkinson's

Parkinson's is characterized not only by motor disturbances, but also by limitations of memory, and so far remained largely unclear how the latter arise. Scientists at the University Medical Center Göttingen have now discovered together with researchers from the Instituto de Medicina Molecular (Lisbon), which molecular process is based on the loss of memory in Parkinson's disease. This opens up new approaches for the treatment of the disease.

The gaps in the memory of Parkinson's disease are, according to the scientists triggered by a protein interactions, which leads to disturbances in the communication between the nerve cells. However, the effect can be remedied by "genetic manipulation and use of antibodies" and restore the memory. The newly discovered molecular pathway could thus be used as a starting point for the treatment of cognitive impairment in Parkinson's disease. The study was published in the journal "Nature Neuroscience".

Researchers have discovered the molecular cause of Parkinson's memory gaps, which also opens new approaches to therapy. (Image: eyeQ / fotolia.com)

Molecular signal path identified

Typical motor symptoms in Parkinson's are the so-called tremor (trembling of the limbs), a stooped posture, difficulty walking and a very limited facial expression. In addition, there are also "deficits in the memory" in the course of the disease "; explain the scientists. However, relatively little was known about the development of these cognitive side effects. In experiments on mice, the researchers from Göttingen and Lisbon have now for the first time been able to demonstrate in detail a molecular signaling pathway that leads to the development of cognitive deficits similar to those in Parkinson's patients.

Fatal interaction between proteins

According to the researchers, the newly discovered signaling pathway is activated by the interaction of abnormal forms of the alpha-synuclein protein with the prion protein (PrPC). It was already known by PrPC "that it is involved in processes that lead to age-related behavioral abnormalities and impairment of memory in neurodegeneration," said the University of Göttingen. The scientists were able to show that the interaction between alpha-synuclein and PrPC initiates a cascade of processes that ultimately leads to disruptions in the contacts between nerve cells (synapses). This affects the communication of the affected nerve cells and favors the development of cognitive deficits.

Parkinson's is much more than a motor disorder

"We now know that Parkinson's disease is much more than a motor disorder"; emphasizes study coordinator Professor dr. Tiago Outeiro, Director of the Department of Experimental Neurodegeneration at the University Medical Center Göttingen. It was already known that certain forms of the alpha-synuclein protein can cause malfunctions in the communication of nerve cells that are responsible for the memory, the expert continued. So far, however, remained unclear how exactly this happens. "Now we know more about the molecular mechanisms. This opens up new therapeutic approaches for the prevention and treatment of Parkinson's disease, "says Prof. Tiago.

New approaches to therapy

The scientists describe in their study for the first time a new "mechanism that is sufficient to initiate early damage to the synapses of nerve cells, which are caused solely by extracellular alpha-synuclein," reports the University of Göttingen. Through the interaction of the proteins, a signal cascade is set in motion which leads to a maladjustment of the calcium budget and a malfunction of the synapses of nerve cells in the brain. Inactivation of the protein by genetic manipulation or the use of antibodies, however, the toxic effect of alpha-synuclein oligomers are repealed, explain the scientists. "In a mouse model of Parkinson's disease, the synaptic and cognitive deficits are eliminated if this signaling pathway is blocked," emphasize Prof. Tiago and colleagues. This opens up completely new approaches to Parkinson's therapy. (Fp)