Study provides new insights into the small acidic protein linked to Parkinson’s disease

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Research by biologists at the University of Buffalo is providing new insights into alpha-synuclein, a small acidic protein associated with Parkinson’s disease.

It is known that alpha-synuclein forms abnormal groups in the brains of Parkinson’s patients, but scientists are still trying to understand how and why this happens.

The new study explores the basic properties of alpha-synuclein, with a focus on a section of the protein known as a non-amyloidal component (NAC). The research was carried out on larvae of fruit flies that were genetically modified to produce normal and mutant forms of human alpha-synuclein.

The study, led by biologist Shermali Gunawardena of the University of Buffalo, was published on January 10 in the journal. Frontiers in Cellular Neuroscience.

Some key findings:

  • The NAC region seems to help alpha-synuclein move through pathways called axons that run from one area from one neuron to another. When the NAC region was missing, alpha-synuclein did not move within the axons.
  • The missing alpha-synuclein in the NAC region can help prevent unwanted aggregates of the protein. In experiments, Gunawardena’s team demonstrated that it is possible, at least in fruit flies, to prevent some key problems that occur when too much alpha-synuclein is produced: protein agglomeration; anomalies in the structure of synapses, which form connections between neurons; and a decrease in the speed at which the larvae crawl. The scientists discovered that when the larvae are designed to produce an excess of alpha-synuclein and a version of alpha-synuclein without the NAC region, the larvae creep normally, the protein is not added and the synapses are normal.

We show that in the larvae of the fruit fly, we can avoid some problems that mimic the symptoms of Parkinson’s disease, such as the accumulation of alpha-synuclein in neurons.

Our work highlights a possible early treatment strategy for Parkinson’s disease that would take advantage of the use of NAC region elimination. One reason why this study is important is because it shows the rescue of alpha-synuclein aggregates, synaptic morphological defects and locomotion defects observed in Parkinson’s disease in the context of a whole organism. “

Shermali Gunawardena, PhD, associate professor of biological sciences at the Faculty of Arts and Sciences of the UB

Source:

Journal reference:

Anderson, E. N. et al. (2020) The region of the non-amyloid component of α-synuclein is important for the transport of α-synuclein within axons. Frontiers in Cellular Neuroscience. doi.org/10.3389/fncel. 2019.00540.

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