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SHR Neuro Krebs Kardio Lipid

Sukseree, S; László, L; Gruber, F; Bergmann, S; Narzt, MS; Nagelreiter, IM; Höftberger, R; Molnár, K; Rauter, G; Birngruber, T; Larue, L; Kovacs, GG; Tschachler, E; Eckhart, L.
Filamentous Aggregation of Sequestosome-1/p62 in Brain Neurons and Neuroepithelial Cells upon Tyr-Cre-Mediated Deletion of the Autophagy Gene Atg7.
Mol Neurobiol. 2018; 55(11):8425-8437 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Autor/innen der Med Uni Graz:
Birngruber Thomas
Rauter Günther

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Number of Figures: 7
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Defects in autophagy and the resulting deposition of protein aggregates have been implicated in aging and neurodegenerative diseases. While gene targeting in the mouse has facilitated the characterization of these processes in different types of neurons, potential roles of autophagy and accumulation of protein substrates in neuroepithelial cells have remained elusive. Here we report that Atg7f/f Tyr-Cre mice, in which autophagy-related 7 (Atg7) is conditionally deleted under the control of the tyrosinase promoter, are a model for accumulations of the autophagy adapter and substrate sequestosome-1/p62 in both neuronal and neuroepithelial cells. In the brain of Atg7f/f Tyr-Cre but not of fully autophagy competent control mice, p62 aggregates were present in sporadic neurons in the cortex and other brain regions as well in epithelial cells of the choroid plexus and the ependyma. Western blot analysis confirmed a dramatic increase of p62 abundance and formation of high-molecular weight species of p62 in the brain of Atg7f/f Tyr-Cre mice relative to Atg7f/f controls. Immuno-electron microscopy showed that p62 formed filamentous aggregates in neurons and ependymal cells. p62 aggregates were also highly abundant in the ciliary body in the eye. Atg7f/f Tyr-Cre mice reached an age of more than 2 years although neurological defects manifesting in abnormal hindlimb clasping reflexes were evident in old mice. These results show that p62 filaments form in response to impaired autophagy in vivo and suggest that Atg7f/f Tyr-Cre mice are a model useful to study the long-term effects of autophagy deficiency on the homeostasis of different neuroectoderm-derived cells.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Autophagy - genetics
Autophagy-Related Protein 7 - genetics
Brain - pathology
Ciliary Body - metabolism
Ependyma - metabolism
Ependyma - pathology
Female -
Gene Deletion -
Integrases - metabolism
Mice -
Neuroepithelial Cells - metabolism
Neuroepithelial Cells - ultrastructure
Neurons - metabolism
Neurons - pathology
Neurons - ultrastructure
Phospholipids - metabolism
Protein Aggregates -
Sequestosome-1 Protein - metabolism
Ubiquitin - metabolism

Find related publications in this database (Keywords)
Protein aggregation
Choroid plexus
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