ArticleHuman molecular genetics2012
Severe disturbance in the Ca2+ signaling in astrocytes from mouse models of human infantile neuroaxonal dystrophy with mutated Pla2g6.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 49 citations in OpenAlex.
- deCLUTTER2+ - a pipeline to analyze calcium traces in a stem cell model for ventral midbrain patterned astrocytes.Disease models & mechanisms · 2023Article
- Modeling the relationship between neuronal activity and the BOLD signal: contributions from astrocyte calcium dynamics.Scientific reports · 2023Article
- Article
- Brain Energy Metabolism: Astrocytes in Neurodegenerative Diseases.CNS neuroscience & therapeutics · 2023Review
- Mouse models of NADK2 deficiency analyzed for metabolic and gene expression changes to elucidate pathophysiology.Human molecular genetics · 2022Article
- Astrocytes, a Promising Opportunity to Control the Progress of Parkinson's Disease.Biomedicines · 2021Review
- Mitochondrial Dysfunction, Oxidative Stress and Neuroinflammation in Neurodegeneration with Brain Iron Accumulation (NBIA).Antioxidants (Basel, Switzerland) · 2020Review
- Substantia nigra echogenicity is associated with serum ferritin, gender and iron-related genes in Parkinson's disease.Scientific reports · 2020Article
- iPLABiochimica et biophysica acta. Molecular and cell biology of lipids · 2019Review
- Mouse germ line mutations due to retrotransposon insertions.Mobile DNA · 2019Review
- Mutations in the Drosophila homolog of human PLA2G6 give rise to age-dependent loss of psychomotor activity and neurodegeneration.Scientific reports · 2018Article
- The Role of Astrocyte Dysfunction in Parkinson's Disease Pathogenesis.Trends in neurosciences · 2017Review
- Mitochondria: A Common Target for Genetic Mutations and Environmental Toxicants in Parkinson's Disease.Frontiers in genetics · 2017Review
- Monozygotic twins with infantile neuroaxonal dystrophy: A case report and literature review.Experimental and therapeutic medicine · 2016Article
- Mitochondrial Ca(2+) Processing by a Unit of Mitochondrial Ca(2+) Uniporter and Na(+)/Ca(2+) Exchanger Supports the Neuronal Ca(2+) Influx via Activated Glutamate Receptors.Neurochemical research · 2016Article
- Review: Insights into molecular mechanisms of disease in neurodegeneration with brain iron accumulation: unifying theories.Neuropathology and applied neurobiology · 2016Review
- Impairment of PARK14-dependent Ca(2+) signalling is a novel determinant of Parkinson's disease.Nature communications · 2016Article
- Mitochondrial dysfunction and defects in lipid homeostasis as therapeutic targets in neurodegeneration with brain iron accumulation.Rare diseases (Austin, Tex.) · 2016Article
- Calcium-independent phospholipases A2 and their roles in biological processes and diseases.Journal of lipid research · 2015Review
- Loss of PLA2G6 leads to elevated mitochondrial lipid peroxidation and mitochondrial dysfunction.Brain : a journal of neurology · 2015Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
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.
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