Lysosomal Storage of Subunit c of Mitochondrial ATP Synthase in Brain-Specific Atp13a2-Deficient Mice

作者：Sato Shigeto; Koike Masato; Funayama Manabu; Ezaki Junji; Fukuda Takahiro; Ueno Takashi; Uchiyama Yasuo; Hattori Nobutaka^*

来源：American Journal Of Pathology, 2016, 186(12): 3074-3082.

DOI：10.1016/j.ajpath.2016.08.006

Kufor-Rakeb syndrome (KRS) is an autosomal recessive form of early-onset parkinsonism linked to the PARK9 locus. The causative gene for KRS is Atp13a2, which encodes a lysosomal type 5 P-type ATPase. We recently showed that KRS/PARK9-linked mutations lead to several lysosomal alterations, including reduced proteolytic processing of cathepsin D in vitro. However, it remains unknown how deficiency of Atp13a2 is connected to lysosomal impairments. To address this issue, we analyzed brain tissues of Atp13a2 conditional-knockout mice, which exhibited characteristic features of neuronal ceroid Lipofuscinosis, including accumulation of Lipofuscin positive for subunit c of mitochondrial ATP synthase, suggesting that a common pathogenic mechanism underlies both neuronal ceroid lipofuscinosis and Parkinson disease.

• 出版日期2016-12