@entity1579 are fatal neurodegenerative and @entity166 for which no therapeutic or prophylactic regimens exist. In search of cellular mechanisms that play a role in prion diseases and have the potential to interfere with accumulation of intracellular pathological prion protein ( @entity27465 ), we investigated the autophagic pathway and one of its recently published inducers, @entity7970 . @entity7970 , an alpha-linked disaccharide, has been shown to accelerate clearance of mutant @entity25864 and alpha-synuclein by activating autophagy, mainly in an @entity3470 -independent manner. Here, we demonstrate that @entity7970 can significantly reduce @entity27465 in a dose- and time-dependent manner while at the same time it induces autophagy in persistently prion-infected neuronal cells. Inhibition of autophagy, either pharmacologically by known autophagy inhibitors like @entity2456 , or genetically by siRNA targeting @entity15254 , counteracted the anti-prion effect of @entity7970 . Hence, we provide direct experimental evidence that induction of autophagy mediates enhanced cellular degradation of prions. Similar results were obtained with @entity3446 , a known inducer of autophagy, and @entity2213 , which has been shown to activate autophagosome formation. While induction of autophagy resulted in reduction of @entity27465 (Sc), inhibition of autophagy increased the amounts of cellular @entity27465 (Sc), suggesting that autophagy is involved in the physiological degradation process of cellular @entity27465 (Sc). Preliminary in vivo studies with @entity7970 in intraperitoneally prion-infected @entity19 did not result in prolongation of incubation times, but demonstrated delayed appearance of @entity27465 (Sc) in the spleen. Overall, our study provides the first experimental evidence for the impact of autophagy in yet another type of @entity179 , namely prion disease.

Autophagy induction by XXXX counteracts cellular prion infection.

@entity7970 :: ('MESH:D014199', 'Chemical') :: ['trehalose', 'Trehalose'] @entity2456 :: ('MESH:C025946', 'Chemical') :: ['3-methyladenine'] @entity15254 :: ('11793(Tax:10090)', 'Gene') :: ['Atg5'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity1579 :: ('MESH:D017096', 'Disease') :: ['Prion diseases'] @entity25864 :: ('15194(Tax:10090)', 'Gene') :: ['huntingtin'] @entity3470 :: ('21977(Tax:10090)', 'Gene') :: ['mTOR'] @entity3446 :: ('MESH:D020123', 'Chemical') :: ['rapamycin'] @entity27465 :: ('19122(Tax:10090)', 'Gene') :: ['PrP(Sc)', 'PrP'] @entity179 :: ('MESH:D019636', 'Disease') :: ['neurodegenerative disease'] @entity166 :: ('MESH:D003141', 'Disease') :: ['infectious disorders'] @entity2213 :: ('MESH:C097613', 'Chemical') :: ['imatinib']
@entity7970 :: (MESH:D014199,Chemical) :: ['trehalose']
