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New screening approach helps track the progression of Parkinson’s disease

Researchers present a new approach to identify molecules involved in the progression of Parkinson’s disease and other neurodegenerative diseases.

When it comes to tracking its progress Parkinson’s disease (PD), there are countless Biomarker investigated. Primarily, the formation of α-synuclein (α-synuclein), an abnormal protein that has been suggested to play a central role in the etiology of PD, has emerged as a potential way to track disease.

However, researchers in studies published in journals Chemical science It was noted that the protein was identified over 20 years ago, but a reliable method of tracking α-synuclein, like other protein aggregates in the brain, has not yet been developed.

To create a viable mechanism for tracking alpha-synuclein, it accompanies Press release Emphasizes the need for a new tracer, a radioactive molecule that clinicians use to image tissues and organs for positron emission tomography (PET). And worked for several years Michael J. Fox Foundation for Parkinson’s Research, Researchers have built an α-synuclein tracer, but could not implement it without data on the structure of the protein.

After the structure of α-synuclein was first announced and more tools were available in the field of computational chemistry, researchers began developing α-synuclein PET tracers. Using a high-throughput calculation method, researchers screened millions of candidate molecules to assess which one binds to a known binding site for α-synuclein.

Their approach is a “model example”, the first way to identify a pseudomolecule that fits perfectly into the binding site. α-synuclein.. Based on this finding, researchers compared this example with real molecules on the market to see which molecules have similar structures.

Their findings screened a small subset of the 20 promising candidates from the first pool of 7 million compounds, and the resulting two compounds had very high binding affinities for α-synuclein. Show

Now that large multicenter grants are available, researchers are leveraging these findings to develop PET tracers for PD and other neurodegenerative diseases. “I really think this is a game that changes the way PET probes are developed,” said research author Dr. Robert Mach, professor of radiology Britton Chance. “The important thing is to be able to screen millions of compounds in a very short time, and to identify a large number of compounds that are likely to bind alpha-synuclein with high affinity, and this same method. Can be applied to the development of other important probes, but presents challenges in the field.

reference

Identification of nanomolar affinity α-synuclein fiber imaging probes by ultra-high throughput in silico screening such as Ferry JJ, Lengyel-Zhand Z, Janssen B. Chem Sci.. Published online on September 10, 2020. doi: 10.1039 / D0SC02159H

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New screening approach helps track the progression of Parkinson’s disease