Functional studies and proteomics in platelets and fibroblasts reveal a lysosomal defect with increased cathepsin-dependent apoptosis in ATP1A3 defective alternating hemiplegia of childhood

• Published in: Journal of proteomics Vol. 86; pp. 53 - 69
• Main Authors: Di Michele, Michela, Goubau, Christophe, Waelkens, Etienne, Thys, Chantal, De Vos, Rita, Overbergh, Lut, Schyns, Tsveta, Buyse, Gunnar, Casaer, Paul, Van Geet, Chris, Freson, Kathleen
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 28.06.2013; Elsevier
• Subjects: adenosinetriphosphatase; Alternating hemiplegia of childhood; Apoptosis; Apoptosis - genetics; Blood Platelets; Blood Platelets - metabolism; Cathepsin; cathepsin B; Cathepsin B - genetics; Cathepsin B - metabolism; childhood; Electrophoresis, Gel, Two-Dimensional; enzymology; Female; Fibroblasts; Fibroblasts - metabolism; gene expression regulation; genetics; granules; Hemiplegia; Hemiplegia - genetics; Hemiplegia - metabolism; Hemiplegia - pathology; heterozygosity; Humans; Infant; Infant, Newborn; Life Sciences; lysosomes; Lysosomes - enzymology; Male; metabolism; missense mutation; pathogenesis; pathology; patients; Platelets; protein synthesis; proteins; Proteomics; Sodium-Potassium-Exchanging ATPase; Sodium-Potassium-Exchanging ATPase - genetics; Transcriptome; Fibroblasts; Cathepsin; Alternating hemiplegia of childhood; Platelets; Proteomics; Apoptosis

Alternating hemiplegia of childhood (AHC) is a rare syndrome with repeated hemiplegic episodes, paroxysmal events and global neurological impairment. Recently, heterozygous de novo ATP1A3 missense mutations have been identified in AHC patients, but the underlying pathogenesis mechanism remains unkno...