Novel protein interactions explain memory deficits in Parkinson's disease

September 26, 2017
The protein alpha-synuclein (green) and PrPc (red) interact in a neuron (yellow dots marked with arrows). Credit: Luísa Lopes Lab, iMM Lisboa

A study published in the journal Nature Neuroscience describes the identification of a novel molecular pathway that can constitute a therapeutic target for cognitive defects in Parkinson's disease. The study showed that abnormal forms of Parkinson's disease (PD)-associated protein alpha-synuclein interact with the prion protein (PrP), triggering a cascade of events that culminates in neuronal dysfunction, causing cognitive defects that are reminiscent of those in PD.

"This is the follow-up of a previous study initiated in my laboratory in which we found that particular forms of the protein alpha-synuclein cause dysfunction of involved in memory formation. We did not know how this was happening. In this new study, we have detailed the molecular mechanisms involved, which suggests we now have new targets for therapeutic intervention," explains Tiago Outeiro.

Using pharmacology and genetics, the team has now defined a series of molecular events that explains the memory defects observed in animals that model some important aspects of PD. Luísa Lopes says, "We used a mouse model of PD in which human alpha-synuclein is produced and found that by blocking this interaction with PrP using a caffeine analogue, reverted the abnormal neuronal activity and memory deficits. This study links nicely with our previous work on Alzheimer's disease, further suggesting that molecules like caffeine may, indeed, have potential benefits against upon neurodegeneration."

Animation shows how novel protein interactions explain memory deficits in Parkinson's disease. Credit: Concept and Animation: Ana de Barros;Images and videos: Luísa Lopes and Tiago Outeiro Lab

Parkinson's disease is a devastating disorder affecting millions of people worldwide. Current therapies are only treat some of the motor symptoms of the disease. "We now know that PD is much more than just a motor disease, and there is a great demand for novel therapies, especially those capable of modulating disease progression or, ideally, capable of preventing the onset of the ," - says Tiago Outeiro.

Calcium levels inside a neuron are demonstrated by an intensity scale where blue is low calcium and red high calcium. Credit: Luísa Lopes lab, iMM Lisboa

"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 (patients and families) affected by these terrible disorders," says Luísa Lopes.

Explore further: Tug of war between Parkinson's protein and growth factor

More information: α-synuclein interacts with PrPC to induce cognitive impairment through mGluR5 and NMDAR2B, Nature Neuroscience (2017). DOI: 10.1038/nn.4648

Related Stories

Tug of war between Parkinson's protein and growth factor

September 18, 2017
Alpha-synuclein, a sticky and sometimes toxic protein involved in Parkinson's disease (PD), blocks signals from an important brain growth factor, Emory researchers have discovered.

Drug discovery: Alzheimer's and Parkinson's spurred by same enzyme

July 3, 2017
Alzheimer's disease and Parkinson's disease are not the same. They affect different regions of the brain and have distinct genetic and environmental risk factors.

Molecular link between Parkinson's disease and prion diseases

September 15, 2017
Parkinson's disease and prion diseases are very different as regards both origins and course. Nonetheless, a research group of SISSA, headed by Professor Giuseppe Legname, has discovered an unexpected and important link between ...

A new insight into Parkinson's disease protein

July 28, 2017
Abnormal clumps of certain proteins in the brain are a prominent feature of Parkinson's and other neurodegenerative diseases, but the role those same proteins might play in the normal brain has been unknown.

Parkinson's is partly an autoimmune disease, study finds

June 21, 2017
Researchers have found the first direct evidence that autoimmunity—in which the immune system attacks the body's own tissues—plays a role in Parkinson's disease, the neurodegenerative movement disorder. The findings raise ...

Recommended for you

Critical toxic species behind Parkinson's disease is glimpsed at work for the first time

December 14, 2017
Researchers have glimpsed how the toxic protein clusters that are associated with Parkinson's Disease disrupt the membranes of healthy brain cells, creating defects in the cell walls and eventually causing a series of events ...

Tapeworm drug could lead the fight against Parkinson's disease

December 12, 2017
Researchers at Cardiff University, in collaboration with the University of Dundee, have identified a drug molecule within a medicine used to treat tapeworm infections which could lead to new treatments for patients with Parkinson's ...

High-intensity exercise delays Parkinson's progression

December 11, 2017
High-intensity exercise three times a week is safe for individuals with early-stage Parkinson's disease and decreases worsening of motor symptoms, according to a new phase 2, multi-site trial led by Northwestern Medicine ...

Changes in diet may improve life expectancy in Parkinson's patients

November 24, 2017
New research from the University of Aberdeen shows that weight loss in people with Parkinson's disease leads to decreased life expectancy, increased risk of dementia and more dependency on care.

Good cells gone bad: Scientists discover PINK-SNO

November 21, 2017
A new study from The Scripps Research Institute (TSRI) is the first to show precisely how a process in nerve cells called the S-nitrosylation (SNO) reaction—which can be caused by aging, pesticides and pollution—may contribute ...

Genetic defects in the cell's 'waste disposal system' linked to Parkinson's disease

November 14, 2017
An international study has shed new light on the genetic factors associated with Parkinson's disease, pointing at a group of lysosomal storage disorder genes as potential major contributors to the onset and progression of ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.