PMID: 18414043Apr 17, 2008Paper

Adaptive autophagy in Alexander disease-affected astrocytes.

Autophagy
Guomei TangJames E Goldman

Abstract

The ubiquitin-proteasome and autophagy-lysosomal pathways are the two main routes of protein and organelle clearance in eukaryotic cells. The proteasome system is responsible for unfolded, short-lived proteins, which precludes the clearance of oligomeric and aggregated proteins, whereas macroautophagy, a process generally referred to as autophagy, mediates mainly the bulk degradation of long-lived cytoplasmic proteins, large protein complexes or organelles.(1) Recently, the autophagy-lysosomal pathway has been implicated in neurodegenerative disorders as an important pathway for the clearance of abnormally accumulated intracellular proteins, such as huntingtin, tau and mutant and modified alpha-synuclein.(1-6) Our recent study illustrated the induction of adaptive autophagy in response to mutant glial fibrillary acidic protein (GFAP) accumulation in astrocytes, in the brains of patients with Alexander disease (AxD), and in mutant GFAP knock-in mouse brains.(7) This autophagic response is negatively regulated by mammalian target of rapamycin (mTOR). The activation of p38 MAPK by GFAP accumulation is responsible for mTOR inactivation and the induction of autophagy. We also found that the accumulation of GFAP impairs proteasome ac...Continue Reading

Citations

Apr 19, 2013·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Tulen PeknyMilos Pekny
Aug 25, 2015·Acta Neuropathologica·Markel OlabarriaJames E Goldman
Dec 18, 2013·Translational Neuroscience·Angela LanciottiElena Ambrosini
Jan 31, 2017·Annual Review of Pathology·Markel Olabarria, James E Goldman

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