Rese­ar­chers have lear­ned more about the true role of alpha-synu­c­lein, a faul­ty pro­te­in invol­ved in the deve­lop­ment of Parkinson’s disea­se. The fin­dings of a recent stu­dy add insight into what goes awry in the brain that leads to the onset of this disea­se.

The stu­dy tit­led, “α‑Synuclein pro­mo­tes dila­ti­on of the exo­cy­to­tic fusi­on pore,” was published in the jour­nal Natu­re Neu­ro­sci­ence.

Rese­ar­chers have known for years that the alpha-synu­c­lein pro­te­in has a cen­tral role in the deve­lop­ment of Parkinson’s disea­se, as its accu­mu­la­ti­on beco­mes toxic to neu­rons. Howe­ver, the real func­tion of this pro­te­in — its role befo­re the disea­se kicks in — pre­vious­ly had been unknown.

“The aggre­ga­ti­on of alpha-synu­c­lein in neu­rons is a hall­mark of Parkinson’s,” Robert Edwards, MD, the study’s aut­hor, said in a news release writ­ten by Wal­lace Rav­ven. “But we wan­ted to search for ear­lier events that might trig­ger the dege­ne­ra­ti­ve pro­cess.”

Pre­vious stu­dies had shown that alpha-synu­c­lein is pre­sent at the syn­ap­ses, the con­nec­tions estab­lished bet­ween neigh­bo­ring neu­rons whe­re the exchan­ge of elec­tri­cal signals and neu­ro­nal com­mu­ni­ca­ti­on takes place.

Using mou­se neu­rons and other cells, rese­ar­chers inves­ti­ga­ted how alpha-synu­c­lein beha­ves at the syn­ap­ses. They found that increa­sing the expres­si­on of this pro­te­in inhi­bits the mecha­nism through which neu­rons release vesi­cles con­tai­ning mole­cu­les to be deli­ve­r­ed to other neu­rons to activa­te them (neu­ro­trans­mit­ters).

In nor­mal levels, howe­ver, alpha-synu­c­lein acce­le­ra­tes the release of the­se mole­cu­les if it is alrea­dy occur­ring.

Several muta­ti­ons in the gene enco­ding alpha-synu­c­lein lead to Parkinson’s disea­se. Accord­ing to Edwards, the­se muta­ti­ons impair the protein’s nor­mal func­tion by alte­ring its par­ti­ci­pa­ti­on in neu­ro­trans­mit­ter release.

“So when the nega­ti­ve effect is intact, but the posi­ti­ve role is blo­cked, the net result dis­rupts neu­ro­trans­mit­ter release,” Edwards said. “This could lead to the impairment in dopa­mi­ne release, and ulti­mate­ly to cell death.”

Dopa­mi­ne is the neu­ro­trans­mit­ter lacking in the brains of pati­ents with Parkinson’s disea­se.

Edwards belie­ves that the­se defec­ts in alpha-synuclein’s mecha­nism of action are the rea­son under­ly­ing several cases of Parkinson’s disea­se that do not invol­ve inheri­ted gene­tic muta­ti­ons. Fur­ther rese­arch is war­ran­ted to under­stand exac­t­ly how alpha-synu­c­lein beco­mes faul­ty under the­se con­di­ti­ons.

“By under­stan­ding the nor­mal func­tion of alpha-synu­c­lein, and in par­ti­cu­lar its regu­la­ti­on, we’re star­ting to under­stand how anyo­ne can acqui­re Parkinson’s disea­se,” Edwards said. “We hope this can help deve­lop the­ra­py that tar­gets the under­ly­ing dege­ne­ra­ti­ve pro­cess.”

Quel­le: https://parkinsonsnewstoday.com/2017/08/07/parkinsons-disease-protein-alpha-synuclein-role-better-understood-following-breakthrough-study/

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