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Article ; Online: Neratinib is a TFEB and TFE3 activator that potentiates autophagy and unbalances energy metabolism in ERBB2+ breast cancer cells.

Bellese, Grazia / Tagliatti, Erica / Gagliani, Maria Cristina / Santamaria, Sara / Arnaldi, Pietro / Falletta, Paola / Rusmini, Paola / Matteoli, Michela / Castagnola, Patrizio / Cortese, Katia

Biochemical pharmacology

2023 Volume 213, Page(s) 115633

Abstract: Neratinib (NE) is an irreversible pan-ERBB tyrosine kinase inhibitor used to treat breast cancers (BCa) with amplification of the ERBB2/HER2/Neu gene or overexpression of the ERBB2 receptor. However, the mechanisms behind this process are not fully ... ...

Abstract	Neratinib (NE) is an irreversible pan-ERBB tyrosine kinase inhibitor used to treat breast cancers (BCa) with amplification of the ERBB2/HER2/Neu gene or overexpression of the ERBB2 receptor. However, the mechanisms behind this process are not fully understood. Here we investigated the effects of NE on critical cell survival processes in ERBB2
MeSH term(s)	Humans ; Female ; Breast Neoplasms/drug therapy ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism ; Receptor, ErbB-2/genetics ; Receptor, ErbB-2/metabolism ; Autophagy ; Energy Metabolism
Chemical Substances	neratinib (JJH94R3PWB) ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; Receptor, ErbB-2 (EC 2.7.10.1) ; TFE3 protein, human ; TFEB protein, human ; ERBB2 protein, human (EC 2.7.10.1)
Language	English
Publishing date	2023-06-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2023.115633
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Article ; Online: Identification of HSPB8 modulators counteracting misfolded protein accumulation in neurodegenerative diseases

Chierichetti, Marta / Cerretani, Mauro / Ciammaichella, Alina / Crippa, Valeria / Rusmini, Paola / Ferrari, Veronica / Tedesco, Barbara / Casarotto, Elena / Cozzi, Marta / Mina, Francesco / Pramaggiore, Paola / Galbiati, Mariarita / Piccolella, Margherita / Bresciani, Alberto / Cristofani, Riccardo / Poletti, Angelo

Life Sciences. 2023 June, v. 322 p.121323-

2023

Abstract: The small Heat Shock Protein B8 (HSPB8) is the core component of the Chaperone-Assisted Selective Autophagy (CASA) complex. This complex selectively targets, transports, and tags misfolded proteins for their recognition by autophagy receptors and ... ...

Abstract	The small Heat Shock Protein B8 (HSPB8) is the core component of the Chaperone-Assisted Selective Autophagy (CASA) complex. This complex selectively targets, transports, and tags misfolded proteins for their recognition by autophagy receptors and insertion into the autophagosome for clearance. CASA is essential to maintain intracellular proteostasis, especially in heart, muscle, and brain often exposed to various types of cell stresses. In neurons, HSPB8 protects against neurotoxicity caused by misfolded proteins in several models of neurodegenerative diseases; by facilitating autophagy, HSPB8 assists misfolded proteins degradation also counteracting proteasome overwhelming and inhibition. To enhance HSPB8 protective activity, we screened a library of approximately 120,000 small molecules to identify compounds capable of increasing HSPB8 gene transcription, translation, or protein stability. We found 83 active compounds active in preliminary dose-response assays and further classified them in 19 chemical classes by medicinal chemists' visual inspection. Of these 19 prototypes, 14 induced HSPB8 mRNA and protein levels in SH-SY5Y cells. Out of these 14 compounds, 3 successfully reduced the aggregation propensity of a disease-associated mutant misfolded superoxide dismutase 1 (SOD1) protein in a flow cytometry-based aggregation assay (Flow cytometric analysis of Inclusions and Trafficking (FloIT)) and induced the expression (mRNA and protein) of some autophagy receptors. Notably, the 3 hits were inactive in HSPB8-depleted cells, confirming that their protective activity is mediated by and requires HSPB8. These compounds may be highly relevant for a therapeutic approach in several human disorders, including neurodegenerative diseases, in which enhancement of CASA exerts beneficial activities.
Keywords	autophagosomes ; brain ; dose response ; flow cytometry ; heart ; heat shock proteins ; humans ; macroautophagy ; muscles ; mutants ; neurotoxicity ; proteasome endopeptidase complex ; superoxide dismutase ; therapeutics ; transcription (genetics) ; HSPB8 ; cancer ; Neurodegenerative disorders ; Neuromuscular disorders ; Chaperone-assisted selective autophagy ; Proteasome
Language	English
Dates of publication	2023-06
Publishing place	Elsevier Inc.
Document type	Article ; Online
Note	Use and reproduction
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2022.121323
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Article ; Online: The Role of Small Heat Shock Proteins in Protein Misfolding Associated Motoneuron Diseases.

Tedesco, Barbara / Ferrari, Veronica / Cozzi, Marta / Chierichetti, Marta / Casarotto, Elena / Pramaggiore, Paola / Mina, Francesco / Galbiati, Mariarita / Rusmini, Paola / Crippa, Valeria / Cristofani, Riccardo / Poletti, Angelo

International journal of molecular sciences

2022 Volume 23, Issue 19

Abstract: Motoneuron diseases (MNDs) are neurodegenerative conditions associated with death of upper and/or lower motoneurons (MNs). Proteostasis alteration is a pathogenic mechanism involved in many MNDs and is due to the excessive presence of misfolded and ... ...

Abstract	Motoneuron diseases (MNDs) are neurodegenerative conditions associated with death of upper and/or lower motoneurons (MNs). Proteostasis alteration is a pathogenic mechanism involved in many MNDs and is due to the excessive presence of misfolded and aggregated proteins. Protein misfolding may be the product of gene mutations, or due to defects in the translation process, or to stress agents; all these conditions may alter the native conformation of proteins making them prone to aggregate. Alternatively, mutations in members of the protein quality control (PQC) system may determine a loss of function of the proteostasis network. This causes an impairment in the capability to handle and remove aberrant or damaged proteins. The PQC system consists of the degradative pathways, which are the autophagy and the proteasome, and a network of chaperones and co-chaperones. Among these components, Heat Shock Protein 70 represents the main factor in substrate triage to folding, refolding, or degradation, and it is assisted in this task by a subclass of the chaperone network, the small heat shock protein (sHSPs/HSPBs) family. HSPBs take part in proteostasis by bridging misfolded and aggregated proteins to the HSP70 machinery and to the degradative pathways, facilitating refolding or clearance of the potentially toxic proteins. Because of its activity against proteostasis alteration, the chaperone system plays a relevant role in the protection against proteotoxicity in MNDs. Here, we discuss the role of HSPBs in MNDs and which HSPBs may represent a valid target for therapeutic purposes.
MeSH term(s)	HSP70 Heat-Shock Proteins/genetics ; HSP70 Heat-Shock Proteins/metabolism ; Heat-Shock Proteins, Small/genetics ; Heat-Shock Proteins, Small/metabolism ; Humans ; Molecular Chaperones/genetics ; Molecular Chaperones/metabolism ; Motor Neuron Disease/metabolism ; Motor Neurons/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Protein Folding ; Proteostasis Deficiencies/metabolism
Chemical Substances	HSP70 Heat-Shock Proteins ; Heat-Shock Proteins, Small ; Molecular Chaperones ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2022-10-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms231911759
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Article ; Online: Valosin Containing Protein (VCP): A Multistep Regulator of Autophagy.

Ferrari, Veronica / Cristofani, Riccardo / Tedesco, Barbara / Crippa, Valeria / Chierichetti, Marta / Casarotto, Elena / Cozzi, Marta / Mina, Francesco / Piccolella, Margherita / Galbiati, Mariarita / Rusmini, Paola / Poletti, Angelo

International journal of molecular sciences

2022 Volume 23, Issue 4

Abstract: Valosin containing protein (VCP) has emerged as a central protein in the regulation of the protein quality control (PQC) system. ...

Abstract	Valosin containing protein (VCP) has emerged as a central protein in the regulation of the protein quality control (PQC) system.
MeSH term(s)	Animals ; Autophagy/physiology ; Humans ; Neurodegenerative Diseases/metabolism ; Neurons/metabolism ; Proteostasis/physiology ; Valosin Containing Protein/metabolism
Chemical Substances	Valosin Containing Protein (EC 3.6.4.6)
Language	English
Publishing date	2022-02-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23041939
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Article ; Online: The role of autophagy-lysosomal pathway in motor neuron diseases.

Tedesco, Barbara / Ferrari, Veronica / Cozzi, Marta / Chierichetti, Marta / Casarotto, Elena / Pramaggiore, Paola / Mina, Francesco / Piccolella, Margherita / Cristofani, Riccardo / Crippa, Valeria / Rusmini, Paola / Galbiati, Mariarita / Poletti, Angelo

Biochemical Society transactions

2022 Volume 50, Issue 5, Page(s) 1489–1503

Abstract: Motor neuron diseases (MNDs) include a broad group of diseases in which neurodegeneration mainly affects upper and/or lower motor neurons (MNs). Although the involvement of specific MNs, symptoms, age of onset, and progression differ in MNDs, the main ... ...

Abstract	Motor neuron diseases (MNDs) include a broad group of diseases in which neurodegeneration mainly affects upper and/or lower motor neurons (MNs). Although the involvement of specific MNs, symptoms, age of onset, and progression differ in MNDs, the main pathogenic mechanism common to most MNDs is represented by proteostasis alteration and proteotoxicity. This pathomechanism may be directly related to mutations in genes encoding proteins involved in the protein quality control system, particularly the autophagy-lysosomal pathway (ALP). Alternatively, proteostasis alteration can be caused by aberrant proteins that tend to misfold and to aggregate, two related processes that, over time, cannot be properly handled by the ALP. Here, we summarize the main ALP features, focusing on different routes utilized to deliver substrates to the lysosome and how the various ALP pathways intersect with the intracellular trafficking of membranes and vesicles. Next, we provide an overview of the mutated genes that have been found associated with MNDs, how these gene products are involved in different steps of ALP and related processes. Finally, we discuss how autophagy can be considered a valid therapeutic target for MNDs treatment focusing on traditional autophagy modulators and on emerging approaches to overcome their limitations.
MeSH term(s)	Humans ; Autophagy/physiology ; Lysosomes/metabolism ; Motor Neuron Disease/genetics ; Motor Neuron Disease/metabolism ; Proteostasis
Language	English
Publishing date	2022-09-29
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	184237-7
ISSN	1470-8752 ; 0300-5127
ISSN (online)	1470-8752
ISSN	0300-5127
DOI	10.1042/BST20220778
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Article ; Online: Identification of HSPB8 modulators counteracting misfolded protein accumulation in neurodegenerative diseases.

Life sciences

2022 Volume 322, Page(s) 121323

Abstract: Aims: The small Heat Shock Protein B8 (HSPB8) is the core component of the Chaperone-Assisted Selective Autophagy (CASA) complex. This complex selectively targets, transports, and tags misfolded proteins for their recognition by autophagy receptors and ... ...

Abstract	Aims: The small Heat Shock Protein B8 (HSPB8) is the core component of the Chaperone-Assisted Selective Autophagy (CASA) complex. This complex selectively targets, transports, and tags misfolded proteins for their recognition by autophagy receptors and insertion into the autophagosome for clearance. CASA is essential to maintain intracellular proteostasis, especially in heart, muscle, and brain often exposed to various types of cell stresses. In neurons, HSPB8 protects against neurotoxicity caused by misfolded proteins in several models of neurodegenerative diseases; by facilitating autophagy, HSPB8 assists misfolded proteins degradation also counteracting proteasome overwhelming and inhibition. Materials and methods: To enhance HSPB8 protective activity, we screened a library of approximately 120,000 small molecules to identify compounds capable of increasing HSPB8 gene transcription, translation, or protein stability. Key findings: We found 83 active compounds active in preliminary dose-response assays and further classified them in 19 chemical classes by medicinal chemists' visual inspection. Of these 19 prototypes, 14 induced HSPB8 mRNA and protein levels in SH-SY5Y cells. Out of these 14 compounds, 3 successfully reduced the aggregation propensity of a disease-associated mutant misfolded superoxide dismutase 1 (SOD1) protein in a flow cytometry-based aggregation assay (Flow cytometric analysis of Inclusions and Trafficking (FloIT)) and induced the expression (mRNA and protein) of some autophagy receptors. Notably, the 3 hits were inactive in HSPB8-depleted cells, confirming that their protective activity is mediated by and requires HSPB8. Significance: These compounds may be highly relevant for a therapeutic approach in several human disorders, including neurodegenerative diseases, in which enhancement of CASA exerts beneficial activities.
MeSH term(s)	Humans ; Autophagy/physiology ; Heat-Shock Proteins/metabolism ; Molecular Chaperones/metabolism ; Motor Neurons/metabolism ; Neuroblastoma/metabolism ; Neurodegenerative Diseases/metabolism ; Protein Folding
Chemical Substances	Heat-Shock Proteins ; HSPB8 protein, human ; Molecular Chaperones
Language	English
Publishing date	2022-12-24
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2022.121323
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Article ; Online: Neurodegenerative Disease-Associated TDP-43 Fragments Are Extracellularly Secreted with CASA Complex Proteins.

Casarotto, Elena / Sproviero, Daisy / Corridori, Eleonora / Gagliani, Maria Cristina / Cozzi, Marta / Chierichetti, Marta / Cristofani, Riccardo / Ferrari, Veronica / Galbiati, Mariarita / Mina, Francesco / Piccolella, Margherita / Rusmini, Paola / Tedesco, Barbara / Gagliardi, Stella / Cortese, Katia / Cereda, Cristina / Poletti, Angelo / Crippa, Valeria

Cells

2022 Volume 11, Issue 3

Abstract: Extracellular vesicles (EVs) play a central role in neurodegenerative diseases (NDs) since they may either spread the pathology or contribute to the intracellular protein quality control (PQC) system for the cellular clearance of NDs-associated proteins. ...

Abstract	Extracellular vesicles (EVs) play a central role in neurodegenerative diseases (NDs) since they may either spread the pathology or contribute to the intracellular protein quality control (PQC) system for the cellular clearance of NDs-associated proteins. Here, we investigated the crosstalk between large (LVs) and small (SVs) EVs and PQC in the disposal of TDP-43 and its FTLD and ALS-associated C-terminal fragments (TDP-35 and TDP-25). By taking advantage of neuronal cells (NSC-34 cells), we demonstrated that both EVs types, but particularly LVs, contained TDP-43, TDP-35 and TDP-25. When the PQC system was inhibited, as it occurs in NDs, we found that TDP-35 and TDP-25 secretion via EVs increased. In line with this observation, we specifically detected TDP-35 in EVs derived from plasma of FTLD patients. Moreover, we demonstrated that both neuronal and plasma-derived EVs transported components of the chaperone-assisted selective autophagy (CASA) complex (HSP70, BAG3 and HSPB8). Neuronal EVs also contained the autophagy-related MAP1LC3B-II protein. Notably, we found that, under PQC inhibition, HSPB8, BAG3 and MAP1LC3B-II secretion paralleled that of TDP-43 species. Taken together, our data highlight the role of EVs, particularly of LVs, in the disposal of disease-associated TDP-43 species, and suggest a possible new role for the CASA complex in NDs.
MeSH term(s)	Adaptor Proteins, Signal Transducing/metabolism ; Amyotrophic Lateral Sclerosis/metabolism ; Apoptosis Regulatory Proteins/metabolism ; Autophagy-Related Proteins/metabolism ; DNA-Binding Proteins/metabolism ; Extracellular Vesicles/metabolism ; Frontotemporal Lobar Degeneration ; Humans ; Molecular Chaperones/metabolism ; Neurodegenerative Diseases ; Peptide Fragments/metabolism
Chemical Substances	Adaptor Proteins, Signal Transducing ; Apoptosis Regulatory Proteins ; Autophagy-Related Proteins ; BAG3 protein, human ; DNA-Binding Proteins ; Molecular Chaperones ; Peptide Fragments ; TARDBP protein, human ; TDP-25 protein, human
Language	English
Publishing date	2022-02-02
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11030516
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Article ; Online: The Role of Sex and Sex Hormones in Neurodegenerative Diseases.

Vegeto, Elisabetta / Villa, Alessandro / Della Torre, Sara / Crippa, Valeria / Rusmini, Paola / Cristofani, Riccardo / Galbiati, Mariarita / Maggi, Adriana / Poletti, Angelo

Endocrine reviews

2019 Volume 41, Issue 2

Abstract: Neurodegenerative diseases (NDs) are a wide class of disorders of the central nervous system (CNS) with unknown etiology. Several factors were hypothesized to be involved in the pathogenesis of these diseases, including genetic and environmental factors. ...

Abstract	Neurodegenerative diseases (NDs) are a wide class of disorders of the central nervous system (CNS) with unknown etiology. Several factors were hypothesized to be involved in the pathogenesis of these diseases, including genetic and environmental factors. Many of these diseases show a sex prevalence and sex steroids were shown to have a role in the progression of specific forms of neurodegeneration. Estrogens were reported to be neuroprotective through their action on cognate nuclear and membrane receptors, while adverse effects of male hormones have been described on neuronal cells, although some data also suggest neuroprotective activities. The response of the CNS to sex steroids is a complex and integrated process that depends on (i) the type and amount of the cognate steroid receptor and (ii) the target cell type-either neurons, glia, or microglia. Moreover, the levels of sex steroids in the CNS fluctuate due to gonadal activities and to local metabolism and synthesis. Importantly, biochemical processes involved in the pathogenesis of NDs are increasingly being recognized as different between the two sexes and as influenced by sex steroids. The aim of this review is to present current state-of-the-art understanding on the potential role of sex steroids and their receptors on the onset and progression of major neurodegenerative disorders, namely, Alzheimer's disease, Parkinson's diseases, amyotrophic lateral sclerosis, and the peculiar motoneuron disease spinal and bulbar muscular atrophy, in which hormonal therapy is potentially useful as disease modifier.
MeSH term(s)	Female ; Gonadal Steroid Hormones/metabolism ; Humans ; Male ; Neurodegenerative Diseases/drug therapy ; Neurodegenerative Diseases/metabolism ; Receptors, Steroid/metabolism ; Sex Characteristics
Chemical Substances	Gonadal Steroid Hormones ; Receptors, Steroid
Language	English
Publishing date	2019-09-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	603096-8
ISSN	1945-7189 ; 0163-769X
ISSN (online)	1945-7189
ISSN	0163-769X
DOI	10.1210/endrev/bnz005
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Article: Retinoic Acid Downregulates HSPB8 Gene Expression in Human Breast Cancer Cells MCF-7.

Piccolella, Margherita / Cristofani, Riccardo / Tedesco, Barbara / Chierichetti, Marta / Ferrari, Veronica / Casarotto, Elena / Cozzi, Marta / Crippa, Valeria / Rusmini, Paola / Galbiati, Mariarita / Poletti, Angelo / Messi, Elio

Frontiers in oncology

2021 Volume 11, Page(s) 652085

Abstract: Breast cancer (BC) is a serious and widespread disease for which different treatments have been developed. In addition to the classic therapies, the treatment with retinoic acid (RA) is still being clinically investigated. RA reduces cancer cells ... ...

Abstract	Breast cancer (BC) is a serious and widespread disease for which different treatments have been developed. In addition to the classic therapies, the treatment with retinoic acid (RA) is still being clinically investigated. RA reduces cancer cells proliferation and migration, but its molecular mechanism of action is not clear. In tumor development, autophagy promotes cancer cell survival and prevents apoptosis. Small heat shock protein B8 (HSPB8) acts together with its co-chaperone BCL-2 associated athanogene 3 (BAG3) stimulating BC proliferation and migration. We analyzed whether direct correlations exist between RA and HSPB8 or BAG3 and how this may play a role in BC. We measured HSPB8 and BAG3 gene expression in MCF-7 BC cells and we analyzed the potential correlation between the antiproliferative and antimigratory effect of RA with the expression level of HSPB8. We found that in MCF-7 cells RA reduces both HSPB8 and BAG3 gene expression and it alters the mitotic spindle organization. Notably, the effects of RA on HSPB8 levels are exerted at both transcriptional and translational levels. RA effects are possibly mediated by miR-574-5p that targets the HSPB8 transcript. Our results suggest that therapeutic doses of RA can efficiently counteract the adverse effects of HSPB8 in BC progression.
Language	English
Publishing date	2021-05-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2021.652085
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Article ; Online: Quantitative assessment of the degradation of aggregated TDP-43 mediated by the ubiquitin proteasome system and macroautophagy.

Cascella, Roberta / Fani, Giulia / Capitini, Claudia / Rusmini, Paola / Poletti, Angelo / Cecchi, Cristina / Chiti, Fabrizio

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2017 Volume 31, Issue 12, Page(s) 5609–5624

Abstract: Amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions are neurodegenerative disorders that share the cytosolic deposition of TDP-43 (TAR DNA-binding protein 43) in the CNS. TDP-43 is well known as being ... ...

Abstract	Amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions are neurodegenerative disorders that share the cytosolic deposition of TDP-43 (TAR DNA-binding protein 43) in the CNS. TDP-43 is well known as being actively degraded by both the proteasome and macroautophagy. The well-documented decrease in the efficiency of these clearance systems in aging and neurodegeneration, as well as the genetic evidence that many of the familial forms of TDP-43 proteinopathies involve genes that are associated with them, suggest that a failure of these protein degradation systems is a major factor that contributes to the onset of TDP-43-associated disorders. Here, we inserted preformed human TDP-43 aggregates in the cytosol of murine NSC34 and N2a cells in diffuse form and observed their degradation under conditions in which exogenous TDP-43 is not expressed and endogenous nuclear TDP-43 is not recruited, thereby allowing a time zero to be established in TDP-43 degradation and to observe its disposal kinetically and analytically. TDP-43 degradation was observed in the absence and presence of selective inhibitors and small interfering RNAs against the proteasome and autophagy. We found that cytosolic diffuse aggregates of TDP-43 can be distinguished in 3 different classes on the basis of their vulnerability to degradation, which contributed to the definition-with previous reports-of a total of 6 distinct classes of misfolded TDP-43 species that range from soluble monomer to undegradable macroaggregates. We also found that the proteasome and macroautophagy-degradable pools of TDP-43 are fully distinguishable, rather than in equilibrium between them on the time scale required for degradation, and that a significant crosstalk exists between the 2 degradation processes.-Cascella, R., Fani, G., Capitini, C., Rusmini, P., Poletti, A., Cecchi, C., Chiti, F. Quantitative assessment of the degradation of aggregated TDP-43 mediated by the ubiquitin proteasome system and macroautophagy.
MeSH term(s)	Animals ; Autophagy/genetics ; Autophagy/physiology ; Cell Line ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Humans ; Inclusion Bodies/metabolism ; Mice ; Motor Neuron Disease/genetics ; Motor Neuron Disease/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Protein Aggregation, Pathological/genetics ; Protein Aggregation, Pathological/metabolism ; Proteolysis ; RNA Interference ; Ubiquitin/genetics ; Ubiquitin/metabolism
Chemical Substances	DNA-Binding Proteins ; TARDBP protein, human ; Ubiquitin ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2017-08-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.201700292RR
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