Promiscuous Roles of Autophagy and Proteasome in Neurodegenerative Proteinopathies
Alterations in autophagy and the ubiquitin proteasome system (UPS) are commonly implicated in protein aggregation and toxicity which manifest in a number of neurological disorders. In fact, both UPS and autophagy alterations are bound to the aggregation, spreading and toxicity of the so-called prion...
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MDPI AG
2020-04-01
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author | Fiona Limanaqi Francesca Biagioni Stefano Gambardella Pietro Familiari Alessandro Frati Francesco Fornai |
author_facet | Fiona Limanaqi Francesca Biagioni Stefano Gambardella Pietro Familiari Alessandro Frati Francesco Fornai |
author_sort | Fiona Limanaqi |
collection | DOAJ |
description | Alterations in autophagy and the ubiquitin proteasome system (UPS) are commonly implicated in protein aggregation and toxicity which manifest in a number of neurological disorders. In fact, both UPS and autophagy alterations are bound to the aggregation, spreading and toxicity of the so-called prionoid proteins, including alpha synuclein (α-syn), amyloid-beta (Aβ), tau, huntingtin, superoxide dismutase-1 (SOD-1), TAR-DNA-binding protein of 43 kDa (TDP-43) and fused in sarcoma (FUS). Recent biochemical and morphological studies add to this scenario, focusing on the coordinated, either synergistic or compensatory, interplay that occurs between autophagy and the UPS. In fact, a number of biochemical pathways such as mammalian target of rapamycin (mTOR), transcription factor EB (TFEB), Bcl2-associated athanogene 1/3 (BAG3/1) and glycogen synthase kinase beta (GSk3β), which are widely explored as potential targets in neurodegenerative proteinopathies, operate at the crossroad between autophagy and UPS. These biochemical steps are key in orchestrating the specificity and magnitude of the two degradation systems for effective protein homeostasis, while intermingling with intracellular secretory/trafficking and inflammatory pathways. The findings discussed in the present manuscript are supposed to add novel viewpoints which may further enrich our insight on the complex interactions occurring between cell-clearing systems, protein misfolding and propagation. Discovering novel mechanisms enabling a cross-talk between the UPS and autophagy is expected to provide novel potential molecular targets in proteinopathies. |
first_indexed | 2024-03-10T20:14:56Z |
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issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-10T20:14:56Z |
publishDate | 2020-04-01 |
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series | International Journal of Molecular Sciences |
spelling | doaj.art-eb014fde3816468b86afae20174ff7da2023-11-19T22:40:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01218302810.3390/ijms21083028Promiscuous Roles of Autophagy and Proteasome in Neurodegenerative ProteinopathiesFiona Limanaqi0Francesca Biagioni1Stefano Gambardella2Pietro Familiari3Alessandro Frati4Francesco Fornai5Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, ItalyI.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli, ItalyI.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli, ItalyDepartment of Human Neurosciences, Division of Neurosurgery, Sapienza University of Rome, 00185 Roma, ItalyI.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli, ItalyDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, ItalyAlterations in autophagy and the ubiquitin proteasome system (UPS) are commonly implicated in protein aggregation and toxicity which manifest in a number of neurological disorders. In fact, both UPS and autophagy alterations are bound to the aggregation, spreading and toxicity of the so-called prionoid proteins, including alpha synuclein (α-syn), amyloid-beta (Aβ), tau, huntingtin, superoxide dismutase-1 (SOD-1), TAR-DNA-binding protein of 43 kDa (TDP-43) and fused in sarcoma (FUS). Recent biochemical and morphological studies add to this scenario, focusing on the coordinated, either synergistic or compensatory, interplay that occurs between autophagy and the UPS. In fact, a number of biochemical pathways such as mammalian target of rapamycin (mTOR), transcription factor EB (TFEB), Bcl2-associated athanogene 1/3 (BAG3/1) and glycogen synthase kinase beta (GSk3β), which are widely explored as potential targets in neurodegenerative proteinopathies, operate at the crossroad between autophagy and UPS. These biochemical steps are key in orchestrating the specificity and magnitude of the two degradation systems for effective protein homeostasis, while intermingling with intracellular secretory/trafficking and inflammatory pathways. The findings discussed in the present manuscript are supposed to add novel viewpoints which may further enrich our insight on the complex interactions occurring between cell-clearing systems, protein misfolding and propagation. Discovering novel mechanisms enabling a cross-talk between the UPS and autophagy is expected to provide novel potential molecular targets in proteinopathies.https://www.mdpi.com/1422-0067/21/8/3028alpha-synucleinamyloid-betatauTDP-43SOD-1FUS |
spellingShingle | Fiona Limanaqi Francesca Biagioni Stefano Gambardella Pietro Familiari Alessandro Frati Francesco Fornai Promiscuous Roles of Autophagy and Proteasome in Neurodegenerative Proteinopathies International Journal of Molecular Sciences alpha-synuclein amyloid-beta tau TDP-43 SOD-1 FUS |
title | Promiscuous Roles of Autophagy and Proteasome in Neurodegenerative Proteinopathies |
title_full | Promiscuous Roles of Autophagy and Proteasome in Neurodegenerative Proteinopathies |
title_fullStr | Promiscuous Roles of Autophagy and Proteasome in Neurodegenerative Proteinopathies |
title_full_unstemmed | Promiscuous Roles of Autophagy and Proteasome in Neurodegenerative Proteinopathies |
title_short | Promiscuous Roles of Autophagy and Proteasome in Neurodegenerative Proteinopathies |
title_sort | promiscuous roles of autophagy and proteasome in neurodegenerative proteinopathies |
topic | alpha-synuclein amyloid-beta tau TDP-43 SOD-1 FUS |
url | https://www.mdpi.com/1422-0067/21/8/3028 |
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