English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Alpha-synuclein (α-syn) pathology is the hallmark of Parkinson‘s disease (PD). The leucine-rich repeat kinase 2 ( LRRK2 ) gene is a major-effect risk gene for sporadic PD (sPD). However, what environmental factors may trigger the formation of α-syn pathology in carriers of  LRRK2  risk variants are still unknown. Here, we report that a markedly increased abundance of  Escherichia coli  ( E .  coli ) in the intestinal microbiota was detected in  LRRK2  risk variant(R1628P or G2385R) carriers with sPD compared with carriers without sPD. Animal experiments showed that  E .  coli  administration triggered pathological α-syn accumulation in the colon and spread to the brain via the gut-brain axis in  Lrrk2  R1628P mice, due to the co-occurrence of  Lrrk2  variant-induced inhibition of α-syn autophagic degradation and increased phosphorylation of α-syn caused by curli in  E .  coli -derived extracellular vesicles. Fecal microbiota transplantation (FMT) effectively ameliorated motor deficits and α-syn pathology in  Lrrk2  R1628P mice. Our findings elaborate on the mechanism that  E. coli  triggers α-syn pathology in  Lrrk2  R1628P mice, and highlight a novel gene-environment interaction pattern in  LRRK2  risk variants. Even more importantly, the findings reveal the interplay between the specific risk gene and the matched environmental factors triggers the initiation of α-syn pathology in sPD.

Escherichia coli triggers α-synuclein pathology in the LRRK2 transgenic mouse model of PD