Open AccessCoenzyme A corrects pathological defects in human neurons of PANK 2‐associated neurodegeneration
Author(s) -
Orellana Daniel I,
Santambrogio Paolo,
Rubio Alicia,
Yekhlef Latefa,
Cancellieri Cinzia,
Dusi Sabrina,
Giannelli Serena G,
Venco Paola,
Mazzara Pietro G,
Cozzi Anna,
Ferrari Maurizio,
Garavaglia Barbara,
Taverna Stefano,
Tiranti Valeria,
Broccoli Vania,
Levi Sonia
Publication year - 2016
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201606391
Subject(s) - neurogenesis , library science , neurodegeneration , neuroscience , biology , medicine , computer science , pathology , disease
Pantothenate kinase‐associated neurodegeneration ( PKAN ) is an early onset and severely disabling neurodegenerative disease for which no therapy is available. PKAN is caused by mutations in PANK 2 , which encodes for the mitochondrial enzyme pantothenate kinase 2. Its function is to catalyze the first limiting step of Coenzyme A (CoA) biosynthesis. We generated induced pluripotent stem cells from PKAN patients and showed that their derived neurons exhibited premature death, increased ROS production, mitochondrial dysfunctions—including impairment of mitochondrial iron‐dependent biosynthesis—and major membrane excitability defects. CoA supplementation prevented neuronal death and ROS formation by restoring mitochondrial and neuronal functionality. Our findings provide direct evidence that PANK 2 malfunctioning is responsible for abnormal phenotypes in human neuronal cells and indicate CoA treatment as a possible therapeutic intervention.