Macroautophagy is not directly involved in the metabolism of amyloid precursor protein.

[gm1 gangliosidosis]

Alterations in the metabolism of amyloid precursor protein (APP ) are believed to play a central role in Alzheimer disease pathogenesis . Burgeoning data indicate that APP is proteolytically processed in endosomal-autophagic-lysosomal compartments . In this study , we used both in vivo and in vitro paradigms to determine whether alterations in macroautophagy affect APP metabolism . Three mouse models of glycosphingolipid storage diseases , namely Niemann-Pick type C 1 , GM 1 gangliosidosis , and Sandhoff disease , had mTOR-independent increases in the autophagic vacuole (AV )-associated protein , LC 3 -II , indicative of impaired lysosomal flux . APP C-terminal fragments (APP -CTFs ) were also increased in brains of the three mouse models ; however , discrepancies between LC 3 -II and APP -CTFs were seen between primary (GM 1 gangliosidosis and Sandhoff disease ) and secondary (Niemann-Pick type C 1 ) lysosomal storage models . APP -CTFs were proportionately higher than LC 3 -II in cerebellar regions of GM 1 gangliosidosis and Sandhoff disease , although LC 3 -II increased before APP -CTFs in brains of NPC 1 mice . Endogenous murine AÎ² 40 from RIPA-soluble extracts was increased in brains of all three mice . The in vivo relationship between AV and APP -CTF accumulation was also seen in cultured neurons treated with agents that impair primary (chloroquine and leupeptin + pepstatin ) and secondary (U 18666 A and vinblastine ) lysosomal flux . However , AÎ² secretion was unaffected by agents that induced autophagy (rapamycin ) or impaired AV clearance , and LC 3 -II -positive AVs predominantly co -localized with degradative LAMP-1 -positive lysosomes . These data suggest that neuronal macroautophagy does not directly regulate APP metabolism but highlights the important anti-amyloidogenic role of lysosomal proteolysis in post-secretase APP -CTF catabolism .

Diseases
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Diseases presenting "neuronal macroautophagy" symptom

gm1 gangliosidosis

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