Common Pathogenic Effects of Missense Mutations in the P-Type ATPase ATP13A2 (PARK9) Associated with Early-Onset Parkinsonism

• Published in: PloS one Vol. 7; no. 6; p. e39942
• Main Authors: Podhajska, Agata, Musso, Alessandra, Trancikova, Alzbeta, Stafa, Klodjan, Moser, Roger, Sonnay, Sarah, Glauser, Liliane, Moore, Darren J.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.06.2012; Public Library of Science (PLoS)
• Subjects: Adenosine triphosphatase; Age; Age of Onset; Analysis; Animals; ATPases; Axonogenesis; Basal ganglia; Bioenergetics; Biology; Brain; Brain diseases; Brain research; Cadmium; Cell Line, Tumor; Central nervous system diseases; Cerebral Cortex - drug effects; Cerebral Cortex - pathology; Endoplasmic reticulum; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - enzymology; Endosomes - drug effects; Endosomes - metabolism; Female; Genetic aspects; Heavy metals; HEK293 Cells; Homozygote; Humans; Intracellular Membranes - drug effects; Intracellular Membranes - enzymology; Laboratories; Life sciences; Localization; Lysosomes - drug effects; Lysosomes - metabolism; Medicine; Membranes; Metals, Heavy - toxicity; Missense mutation; Morphology; Movement disorders; Mutants; Mutation; Mutation, Missense - genetics; Nervous system diseases; Neurites - drug effects; Neurites - metabolism; Neurons; Neurotoxicity; Nickel; Oxidative stress; Parkinson disease; Parkinson's disease; Parkinsonian Disorders - enzymology; Parkinsonian Disorders - genetics; Proteasome Endopeptidase Complex - drug effects; Proteasome Endopeptidase Complex - metabolism; Proteasomes; Protein Stability - drug effects; Protein Transport - drug effects; Proteins; Proteolysis - drug effects; Proton-Translocating ATPases - genetics; Rats; Rats, Sprague-Dawley; Rodents; Sensitizing; Stability; Toxicity; Transgenic animals; Switzerland

Mutations in the ATP13A2 gene (PARK9) cause autosomal recessive, juvenile-onset Kufor-Rakeb syndrome (KRS), a neurodegenerative disease characterized by parkinsonism. KRS mutations produce truncated forms of ATP13A2 with impaired protein stability resulting in a loss-of-function. Recently, homozygou...