Mechanism for the Spread of Lewy Bodies

Parkinson's disease and Lewy body disease are caused by Lewy bodies, which are clumps of an abnormally folded protein known as alpha-synuclein. The idea that alpha-synuclein might spread from neuron to neuron arose when fetal nerve tissue was transplanted into patients with Parkinson's and then that tissue developed Lewy bodies. This indicated that nearby diseased cells had infected the transplanted tissue. Studies subsequently showed that alpha-synuclein can spread between neighboring cells and cause cell death. Subsequent studies with mice showed that the spread of alpha-synuclein could account for the damage typical of Parkinson's disease.

In a study published in September 2014, a team from the Medical University of Vienna demonstrated the cell-to-cell transmission of alpha-synuclein in the human brain. In collaboration with researchers from the USA, Germany, and Hungary, they were able to observe the uptake of the pathological form of alpha-synuclein by nerve cells and its spread from cell to cell. This infection process can account for the deterioration of patients with Parkinson's and Lewy body disease. The hope is that treatment can be developed that prevents the cell-to-cell transmission.

Scientists were able to follow the spread of alpha-synuclein by using a new antibody that was developed to distinguish between the form of alpha-synuclein that occurs normally and the abnormal, disease-causing form. It may also be possible to use this antibody to detect the presence of abnormal alpha-synuclein in the cerebrospinal fluid, thus facilitating disease diagnosis.

A press release about the study is available. The abstract of the scientific paper published in Neurobiology of Disease is also available.

The Purpose of Normal Alpha-Synuclein

As has been noted, Parkinson's disease and Lewy body disease are caused by abnormal alpha-synuclein that clumps into Lewy bodies. A normal form of alpha-synuclein exists in everyone's brain, thus, the question arises as to what its purpose is. Understanding its normal role could help understand the abnormal form.

A team at the University of California, San Diego, School of Medicine first confirmed what others have found: alpha-synuclein assembles into aggregates at nerve synapses. The synapses are the points at which nerve cells communicate with one another by means of chemicals known as neurotransmitters. By bunching up at synapses, alpha-synuclein seems to act as a brake by reducing the release of neurotransmitters. The alpha-synuclein is now thought to play a role in managing the communication among nerve cells.

A press release about the study is available. The abstract of the scientific paper published in Current Biology is also available.