The autophagy/lysosome pathway is impaired in SCA7 patients and SCA7 knock-in mice
By Alves S, Cormier-Dequaire F*, Marinello M*, Marais T, Muriel MP, Beaumatin F, Chrabonnier-Beaupel F, Tahiri K, Seilhean D, El-Hachimi KH, Ruberg M, Stevanin G, Barkats M, den Dunnen W, Priault M, Brice A, Durr A, Corvol JC, Sittler A (* co-second authors).
Acta Neuropathol 2014 (advance online May 24).
We provide evidence that the autophagy/lysosome pathway is impaired in neurons undergoing degeneration in SCA7, using genetic and functionnal studies in vitro and in vivo, in patients and in mouse.
Autophagy/lysosome-associated molecules might, therefore, be useful markers for monitoring the effects of potential therapeutic approaches
F igure 6. Ultrastructural analysis of autophagy in the cerebellum of late stage SC A7 K I mice.
Representative electron micrographs from a SCA7 KI (b,e-h) mouse and a WT (a,c,d) littermate. a Nucleus and
cytoplasm of a WT PC. b Dark cell degeneration in a SCA7 KI PC. c Normal Golgi apparatus with small
secretory vesicles and a small structure containing a few vesicles (arrow). d Primary lysosome in a WT PC
with normal morphology containing fine, granular material (arrow). e Lysosome with electron-dense content in
the lumen (asterisk) and a multi-vesicular body (arrow). f Two multi-vesicular bodies (arrows) were detected in
close proximity in a SCA7 KI PC. g Autolysosome containing amorphous electron-dense material (arrow) and
lipids (clear space). h Autolysosome (arrow) containing an autophagic vacuole with a lipid droplet (clear space)
and granular electron-dense material. Autolysosome associated with a mitochondrion (arrowhead) and a multilamellar
body (asterisk). Bars: 5μm (a,b); 500nm (c-h). All data are from 11-week-old mice (3 mice/group).