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

Infantile neuroaxonal dystrophy (INAD; OMIM #no. 256600) is an inherited degenerative nervous system disorder characterized by nerve abnormalities in brain, spinal cord and peripheral nerves. About 85% of INAD patients carry mutations in the  PLA2G6  gene that encodes for a Ca 2+ -independent phospholipase A 2  (VIA iPLA 2 ), but how these mutations lead to disease is unknown. Besides regulating phospholipid homeostasis, VIA iPLA 2  is emerging with additional non-canonical functions, such as modulating store-regulated Ca 2+  entry into cells, and mitochondrial functions. In turn, defective Ca 2+  regulation could contribute to the development of INAD. Here, we studied possible changes in ATP-induced Ca 2+  signaling in astrocytes derived from two mutant strains of mice. The first strain carries a hypomorphic allele of the  Pla2g6  that reduces transcript levels to 5–10% of that observed in wild-type mice. The second strain carries a point mutation in  Pla2g6  that results in inactive VIA iPLA 2  protein with postulated gain in toxicity. Homozygous mice from both strains develop pathology analogous to that observed in INAD patients. The nucleotide ATP is the most important transmitter inducing Ca 2+  signals in astroglial networks. We demonstrate here a severe disturbance in Ca 2+  responses to ATP in astrocytes derived from both mutant mouse strains. The duration of the Ca 2+  responses in mutant astrocytes was significantly reduced when compared with values observed in control cells. We also show that the reduced Ca 2+  responses are probably due to a reduction in capacitative Ca 2+  entry (2.3-fold). Results suggest that altered Ca 2+  signaling could be a central mechanism in the development of INAD pathology.

Severe disturbance in the Ca 2+ signaling in astrocytes from mouse models of human infantile neuroaxonal dystrophy with mutated Pla2g6