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/

Zendy Plus

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

Zendy Tools

Zendy Open

Disruption of the blood-brain barrier (BBB) is a serious complication frequently encountered in neurodegenerative disorders. Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating childhood neurodegenerative lysosomal storage disorder caused by palmitoyl-protein thioesterase-1 (PPT1) deficiency. It remains unclear whether BBB is disrupted in INCL and if so, what might be the molecular mechanism(s) of this complication. We previously reported that the  Ppt1 -knockout ( Ppt1 -KO) mice that mimic INCL manifest high levels of oxidative stress and neuroinflammation. Recently, it has been reported that CD4 +  T-helper 17 (T H 17) lymphocytes may mediate BBB disruption and neuroinflammation, although the precise molecular mechanism(s) remain unclear. We sought to determine: (i) whether the BBB is disrupted in  Ppt1 -KO mice, (ii) if so, do T H 17-lymphocytes underlie this complication, and (iii) how might T H 17 lymphocytes breach the BBB. Here, we report that the BBB is disrupted in  Ppt1 -KO mice and that T H 17 lymphocytes producing IL-17A mediate disruption of the BBB by stimulating production of matrix metalloproteinases (MMPs), which degrade the tight junction proteins essential for maintaining BBB integrity. Importantly, dietary supplementation of resveratrol (RSV), a naturally occurring antioxidant/anti-inflammatory polyphenol, markedly reduced the levels of T H 17 cells, IL-17A and MMPs, and elevated the levels of tight junction proteins, which improved the BBB integrity in  Ppt1 -KO mice. Intriguingly, we found that RSV suppressed the differentiation of CD4 +  T lymphocytes to IL-17A-positive T H 17 cells. Our findings uncover a mechanism by which T H 17 lymphocytes mediate BBB disruption and suggest that small molecules such as RSV that suppress T H 17 differentiation are therapeutic targets for neurodegenerative disorders such as INCL.

The blood-brain barrier is disrupted in a mouse model of infantile neuronal ceroid lipofuscinosis: amelioration by resveratrol