calpain and Pantothenate-Kinase-Associated-Neurodegeneration

Pantothenate Kinase-associated Neurodegeneration (PKAN) belongs to a wide spectrum of diseases characterized by brain iron accumulation and extrapyramidal motor signs. PKAN is caused by mutations in PANK2, encoding the mitochondrial pantothenate kinase 2, which is the first enzyme of the biosynthesis of Coenzyme A. We established and characterized glutamatergic neurons starting from previously developed PKAN Induced Pluripotent Stem Cells (iPSCs). Results obtained by inductively coupled plasma mass spectrometry indicated a higher amount of total cellular iron in PKAN glutamatergic neurons with respect to controls. PKAN glutamatergic neurons, analyzed by electron microscopy, exhibited electron dense aggregates in mitochondria that were identified as granules containing calcium phosphate. Calcium homeostasis resulted compromised in neurons, as verified by monitoring the activity of calcium-dependent enzyme calpain1, calcium imaging and voltage dependent calcium currents. Notably, the presence of calcification in the internal

Topics: Adolescent; Brain; Calcium; Calpain; Child; Child, Preschool; Cohort Studies; Cytoplasm; Female; Homeostasis; Humans; Induced Pluripotent Stem Cells; Infant; Iron; Magnetic Resonance Imaging; Male; Mass Spectrometry; Microscopy, Electron; Mitochondria; Neurons; Pantothenate Kinase-Associated Neurodegeneration; Phosphotransferases (Alcohol Group Acceptor); Tomography, X-Ray Computed; Young Adult