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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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Autores principales: Limanaqi, Fiona, Biagioni, Francesca, Gambardella, Stefano, Familiari, Pietro, Frati, Alessandro, Fornai, Francesco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215558/
https://www.ncbi.nlm.nih.gov/pubmed/32344772
http://dx.doi.org/10.3390/ijms21083028
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author Limanaqi, Fiona
Biagioni, Francesca
Gambardella, Stefano
Familiari, Pietro
Frati, Alessandro
Fornai, Francesco
author_facet Limanaqi, Fiona
Biagioni, Francesca
Gambardella, Stefano
Familiari, Pietro
Frati, Alessandro
Fornai, Francesco
author_sort Limanaqi, Fiona
collection PubMed
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.
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spelling pubmed-72155582020-05-22 Promiscuous Roles of Autophagy and Proteasome in Neurodegenerative Proteinopathies Limanaqi, Fiona Biagioni, Francesca Gambardella, Stefano Familiari, Pietro Frati, Alessandro Fornai, Francesco Int J Mol Sci Review 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. MDPI 2020-04-24 /pmc/articles/PMC7215558/ /pubmed/32344772 http://dx.doi.org/10.3390/ijms21083028 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Limanaqi, Fiona
Biagioni, Francesca
Gambardella, Stefano
Familiari, Pietro
Frati, Alessandro
Fornai, Francesco
Promiscuous Roles of Autophagy and Proteasome in Neurodegenerative Proteinopathies
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 Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215558/
https://www.ncbi.nlm.nih.gov/pubmed/32344772
http://dx.doi.org/10.3390/ijms21083028
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