論文雑誌「Brain」のカバーアートを制作しました［順天堂大学］
弊社で制作しました順天堂大学 脳神経内科
波田野 琢先生のカバーアートが
オックスフォード大学出版局発行の学術雑誌 Brain 2020年4月号の
Front Coverに選ばれました。
Client
順天堂大学
脳神経内科
波田野 琢 先生
脳神経内科
波田野 琢 先生
Journal
Brain：A Journal of Neurology
April 2020 Volume 143,Issue 4 Link
April 2020 Volume 143,Issue 4 Link
Variants in saposin D domain of prosaposin gene linked to Parkinson’s disease
Yutaka Oji, Taku Hatano, Shin-Ichi Ueno, Manabu Funayama, Kei-ichi Ishikawa, Ayami Okuzumi, Sachiko Noda, Shigeto Sato, Wataru Satake, Tatsushi Toda ... Show more
Brain, Volume 143, Issue 4, April 2020, Pages 1190–1205,
Link
Abstract
Recently, the genetic variability in lysosomal storage disorders has been implicated in the pathogenesis of Parkinson’s disease. Here, we found that variants in prosaposin (PSAP), a rare causative gene of various types of lysosomal storage disorders, are linked to Parkinson’s disease. Genetic mutation screening revealed three pathogenic mutations in the saposin D domain of PSAP from three families with autosomal dominant Parkinson’s disease. Whole-exome sequencing revealed no other variants in previously identified Parkinson’s disease-causing or lysosomal storage disorder-causing genes. A case-control association study found two variants in the intronic regions of the PSAP saposin D domain (rs4747203 and rs885828) in sporadic Parkinson’s disease had significantly higher allele frequencies in a combined cohort of Japan and Taiwan. We found the abnormal accumulation of autophagic vacuoles, impaired autophagic flux, altered intracellular localization of prosaposin, and an aggregation of α-synuclein in patient-derived skin fibroblasts or induced pluripotent stem cell-derived dopaminergic neurons. In mice, a Psap saposin D mutation caused progressive motor decline and dopaminergic neurodegeneration. Our data provide novel genetic evidence for the involvement of the PSAP saposin D domain in Parkinson’s disease.
Yutaka Oji, Taku Hatano, Shin-Ichi Ueno, Manabu Funayama, Kei-ichi Ishikawa, Ayami Okuzumi, Sachiko Noda, Shigeto Sato, Wataru Satake, Tatsushi Toda ... Show more
Brain, Volume 143, Issue 4, April 2020, Pages 1190–1205,
Link
Abstract
Recently, the genetic variability in lysosomal storage disorders has been implicated in the pathogenesis of Parkinson’s disease. Here, we found that variants in prosaposin (PSAP), a rare causative gene of various types of lysosomal storage disorders, are linked to Parkinson’s disease. Genetic mutation screening revealed three pathogenic mutations in the saposin D domain of PSAP from three families with autosomal dominant Parkinson’s disease. Whole-exome sequencing revealed no other variants in previously identified Parkinson’s disease-causing or lysosomal storage disorder-causing genes. A case-control association study found two variants in the intronic regions of the PSAP saposin D domain (rs4747203 and rs885828) in sporadic Parkinson’s disease had significantly higher allele frequencies in a combined cohort of Japan and Taiwan. We found the abnormal accumulation of autophagic vacuoles, impaired autophagic flux, altered intracellular localization of prosaposin, and an aggregation of α-synuclein in patient-derived skin fibroblasts or induced pluripotent stem cell-derived dopaminergic neurons. In mice, a Psap saposin D mutation caused progressive motor decline and dopaminergic neurodegeneration. Our data provide novel genetic evidence for the involvement of the PSAP saposin D domain in Parkinson’s disease.
