ATP13A2 deficiency induces a decrease in cathepsin D activity, fingerprint-like inclusion body formation, and selective degeneration of dopaminergic neurons

作者：Matsui Hideaki; Sato Fumiaki; Sato Shigeto; Koike Masato; Taruno Yosuke; Saiki Shinji; Funayama Manabu; Ito Hidefumi; Taniguchi Yoshihito; Uemura Norihito; Toyoda Atsushi; Sakaki Yoshiyuki; Takeda Shunichi; Uchiyama Yasuo; Hattori Nobutaka^*; Takahashi Ryosuke

来源：FEBS LETTERS, 2013, 587(9): 1316-1325.

DOI：10.1016/j.febslet.2013.02.046

• Parkinson%26apos
• s disease
• Medaka fish
• ATP13A2
• Lysosome

Kufor-Rakeb syndrome (KRS) was originally described as an autosomal recessive form of early-onset parkinsonism with pyramidal degeneration and dementia. ATP13A2 was identified as the causative gene in KRS. ATP13A2 encodes the ATP13A2 protein, which is a lysosomal type5 P-type ATPase, and ATP13A2 mutations are linked to autosomal recessive familial parkinsonism. %26lt;br%26gt;Here, we report that normal ATP13A2 localizes in the lysosome, whereas disease-associated variants remain in the endoplasmic reticulum. Cathepsin D activity was decreased in ATP13A2-knockdown cells that displayed lysosome-like bodies characterized by fingerprint-like structures. Furthermore, an atp13a2 mutation in medaka fish resulted in dopaminergic neuronal death, decreased cathepsin D activity, and fingerprint-like structures in the brain. Based on these results, lysosome abnormality is very likely to be the primary cause of KRS/PARK9.

• 出版日期2013-5-2