Neuronal cell death in transmissible spongiform encephalopathies (prion diseases) revisited: from apoptosis to autophagy

Liberski, Paweł P.; Sikorska, Beata; Bratosiewicz-Wąsik, Jolanta; Gajdusek, D. Carleton; Brown, Paul

doi:10.1016/j.biocel.2004.04.016

Cited by 104 publications

(84 citation statements)

References 116 publications

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“…Ultrastructural evidence for autophagy was initially described in animals and then humans with prion disease (for review, see Liberski et al, 2004). Induction of autophagy in experimental models of prion disease has also been attempted, although the results have been mixed.…”

Section: Discussionmentioning

confidence: 99%

Rapamycin Delays Disease Onset and Prevents PrP Plaque Deposition in a Mouse Model of Gerstmann–Sträussler–Scheinker Disease

et al. 2012

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Autophagy is a cell survival response to nutrient deprivation that delivers cellular components to lysosomes for digestion. In recent years, autophagy has also been shown to assist in the degradation of misfolded proteins linked to neurodegenerative disease (Ross and Poirier, 2004). In support of this, rapamycin, an autophagy inducer, improves the phenotype of several animal models of neurodegenerative disease. Our Tg(PrP-A116V) mice model Gerstmann-Sträussler-Scheinker disease (GSS), a genetic prion disease characterized by prominent ataxia and extracellular PrP amyloid plaque deposits in brain (Yang et al., 2009). To determine whether autophagy induction can mitigate the development of GSS, Tg(PrP-A116V) mice were chronically treated with 10 or 20 mg/kg rapamycin intraperitoneally thrice weekly, beginning at 6 weeks of age. We observed a dose-related delay in disease onset, a reduction in symptom severity, and an extension of survival in rapamycin-treated Tg(PrP-A116V) mice. Coincident with this response was an increase in the autophagy-specific marker LC3II, a reduction in insoluble PrP-A116V, and a near-complete absence of PrP amyloid plaques in the brain. An increase in glial cell apoptosis of unclear significance was also detected. These findings suggest autophagy induction enhances elimination of misfolded PrP before its accumulation in plaques. Because ataxia persisted in these mice despite the absence of plaque deposits, our findings also suggest that PrP plaque pathology, a histopathological marker for the diagnosis of GSS, is not essential for the GSS phenotype.

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Section: Discussionmentioning

confidence: 99%

Rapamycin Delays Disease Onset and Prevents PrP Plaque Deposition in a Mouse Model of Gerstmann–Sträussler–Scheinker Disease

et al. 2012

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“…41 However, data on autophagy in prion diseases are still very limited. [13][14][15][16][17][42][43][44] Electron microscopy studies pointed towards a possible contribution of autophagy in prion disease-associated neurodegeneration, whereas others observed in Autophagy and cellular prion infection www.landesbioscience.com Autophagy(30 and 60 days), this effect was not evident at later time points (e.g., 90 days p.i. ), and prion incubation times of trehalose-and sucrose-treated animals were not different from that of mock-treated mice.…”

Section: Discussionmentioning

confidence: 99%

Autophagy induction by trehalose counter-acts cellular prion-infection

Aguib

Heiseke²,

Gilch³

et al. 2009

Autophagy

204

159

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“…They include spongiform change, astro-and microglial proliferation, amyloid plaques in a proportion of cases and neuronal drop-out [20]. Neurons degenerate and die by either apoptosis or autophagy, or both [6,7,14,15]. A novel prion disease with autonomic disturbances and diarrhea was recently described [20].…”

Section: Introductionmentioning

confidence: 99%

Robust autophagy in optic nerves of experimental Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker disease

Liberski¹,

Gajos²,

Bogucki³

2017

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Neuronal cell death in transmissible spongiform encephalopathies (prion diseases) revisited: from apoptosis to autophagy

Cited by 104 publications

References 116 publications

Rapamycin Delays Disease Onset and Prevents PrP Plaque Deposition in a Mouse Model of Gerstmann–Sträussler–Scheinker Disease

Rapamycin Delays Disease Onset and Prevents PrP Plaque Deposition in a Mouse Model of Gerstmann–Sträussler–Scheinker Disease

Autophagy induction by trehalose counter-acts cellular prion-infection

Robust autophagy in optic nerves of experimental Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker disease

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