Alpa-synuclein Research in 2 offerings

[Sapeye2020]

I stumbled onto this page from Bulgaria but tried to find the ORIGINAL work report but ended up with nothing.

novinite.com/articles/19918...

It appears to be recent as you can see

AND "The tiny bubbles that may spread Parkinson’s disease"

found here parkinsonpost.com/the-tiny-... from Parkinson's Canada

I tried to find the original posting date but ???

[ElliotGreen]

The first news article you linked to referenced an author, a publication, and the topic (alpha-synuclein and DNA repair). I searched at Google scholar and found this. Very interesting.

nature.com/articles/s41598-...

TITLE:

Alpha-synuclein is a DNA binding protein that modulates DNA repair with implications for Lewy body disorders

ABSTRACT:

Alpha-synuclein is a presynaptic protein that forms abnormal cytoplasmic aggregates in Lewy body disorders. Although nuclear alpha-synuclein localization has been described, its function in the nucleus is not well understood. We demonstrate that alpha-synuclein modulates DNA repair. First, alpha-synuclein colocalizes with DNA damage response components within discrete foci in human cells and mouse brain. Removal of alpha-synuclein in human cells leads to increased DNA double-strand break (DSB) levels after bleomycin treatment and a reduced ability to repair these DSBs. Similarly, alpha-synuclein knock-out mice show increased neuronal DSBs that can be rescued by transgenic reintroduction of human alpha-synuclein. Alpha-synuclein binds double-stranded DNA and helps to facilitate the non-homologous end-joining reaction. Using a new, in vivo imaging approach that we developed, we find that serine-129-phosphorylated alpha-synuclein is rapidly recruited to DNA damage sites in living mouse cortex. We find that Lewy inclusion-containing neurons in both mouse model and human-derived patient tissue demonstrate increased DSB levels. Based on these data, we propose a model whereby cytoplasmic aggregation of alpha-synuclein reduces its nuclear levels, increases DSBs, and may contribute to programmed cell death via nuclear loss-of-function. This model could inform development of new treatments for Lewy body disorders by targeting alpha-synuclein-mediated DNA repair mechanisms.

[jeffreyn in reply to ElliotGreen]

See also this SoPD blog post from Simon:

scienceofparkinsons.com/201...

[ElliotGreen in reply to jeffreyn]

"Interestingly, in both a mouse model of Parkinson’s (the preformed fibril model) and in post mortem human brain tissue from people who passed away with Parkinsons, the researchers found that alpha synuclein pathology was associated with evidence of increased DNA damage.

"All of these results suggested to the researchers that when alpha synuclein is clustered or aggregated together (and forming Lewy bodies) in affected neurons, this leads to decreases in levels of the protein in the nucleus. And as a result of this reduction in levels of alpha synuclein in the nucleus, there is more risk of DNA damage."