Abstract representation of a cell.

Stem cell research on Parkinson’s

Activation of transposable elements as triggers of neuroinflammation in Parkinson’s disease

Recent stu­dies in the field of Parkinson’s dise­a­se have incre­asing­ly focu­sed on the role of neu­ro­in­flamm­a­ti­on in the patho­ge­ne­sis of the dise­a­se. In this pro­ject we stu­dy the fac­tors invol­ved in neu­ro­in­flamm­a­ti­on in Parkinson’s dise­a­se using com­plex in vitro models con­tai­ning human neu­rons, astro­cytes and microglia.

Ratio­na­le for the stu­dy: Inflamm­a­ti­on is a com­mon event in Parkinson’s dise­a­se (PD), but its source remains unclear. The­re are many can­di­da­tes that could cau­se inflamm­a­ti­on in the ner­vous sys­tem. A likely can­di­da­te invol­ves the acti­vi­ty of trans­posable ele­ments, which are virus-like gene frag­ments left over from viral infec­tions. While trans­posable ele­ments are nor­mal­ly inac­ti­ve, cer­tain stres­sors can reac­ti­va­te the­se genes, lea­ding to a poten­ti­al immu­ne respon­se, inclu­ding inflammation.

Hypo­the­sis: This stu­dy aims to deter­mi­ne whe­ther trans­posable ele­ments are acti­ve in tis­sues of pati­ents with Parkinson’s dise­a­se and whe­ther this acti­vi­ty can indu­ce inflamm­a­ti­on in the ner­vous system.

Stu­dy design: We will first look for evi­dence of trans­posable ele­ment acti­vi­ty using sin­gle-cell RNA sequen­cing of tis­sues from peo­p­le with Parkinson’s dise­a­se. This par­ti­cu­lar expe­ri­ment will also allow us to deter­mi­ne whe­ther pati­ent cells that show increased trans­posable ele­ment acti­vi­ty also show increased signs of inflamm­a­ti­on. Becau­se cen­tral ner­vous sys­tem cells (neu­rons, astro­cytes, and micro­glia) can be grown in a labo­ra­to­ry cul­tu­re sys­tem, we can also test whe­ther mani­pu­la­ti­ons that indu­ce the acti­vi­ty of trans­posable ele­ments in the­se cells also eli­cit an immu­ne respon­se that would result in inflamm­a­ti­on. This would sug­gest that blo­cking trans­po­son acti­vi­ty could block inflammation.

Impli­ca­ti­ons for Parkinson’s dise­a­se diagnosis/treatment: If we can deter­mi­ne that trans­posable ele­ment acti­vi­ty is the trig­ger for inflamm­a­ti­on in Parkinson’s dise­a­se, this would open up seve­ral unex­plo­red tre­at­ment opti­ons. This would allow the tar­ge­ted deve­lo­p­ment of anti-inflamm­a­to­ry or anti­vi­ral com­pounds that are acti­ve against the spe­ci­fic trig­gers obser­ved in samples from Parkinson’s patients.

Project Results

This pro­ject, inves­ti­ga­ting an enti­re­ly new patho­ge­nic mecha­nism in PD, has the poten­ti­al to open a num­ber of new ave­nues of PD rese­arch with clear cli­ni­cal rele­van­ce, inclu­ding both dia­gno­stics and therapeutics.




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