Cargando…
The Neuroendocrine Protein 7B2 Suppresses the Aggregation of Neurodegenerative Disease-related Proteins
Neurodegenerative diseases such as Alzheimer (AD) and Parkinson (PD) are characterized by abnormal aggregation of misfolded β-sheet-rich proteins, including amyloid-β (Aβ)-derived peptides and tau in AD and α-synuclein in PD. Correct folding and assembly of these proteins are controlled by ubiquitou...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542996/ https://www.ncbi.nlm.nih.gov/pubmed/23172224 http://dx.doi.org/10.1074/jbc.M112.417071 |
_version_ | 1782255602254217216 |
---|---|
author | Helwig, Michael Hoshino, Akina Berridge, Casey Lee, Sang-Nam Lorenzen, Nikolai Otzen, Daniel E. Eriksen, Jason L. Lindberg, Iris |
author_facet | Helwig, Michael Hoshino, Akina Berridge, Casey Lee, Sang-Nam Lorenzen, Nikolai Otzen, Daniel E. Eriksen, Jason L. Lindberg, Iris |
author_sort | Helwig, Michael |
collection | PubMed |
description | Neurodegenerative diseases such as Alzheimer (AD) and Parkinson (PD) are characterized by abnormal aggregation of misfolded β-sheet-rich proteins, including amyloid-β (Aβ)-derived peptides and tau in AD and α-synuclein in PD. Correct folding and assembly of these proteins are controlled by ubiquitously expressed molecular chaperones; however, our understanding of neuron-specific chaperones and their involvement in the pathogenesis of neurodegenerative diseases is limited. We here describe novel chaperone-like functions for the secretory protein 7B2, which is widely expressed in neuronal and endocrine tissues. In in vitro experiments, 7B2 efficiently prevented fibrillation and formation of Aβ(1–42), Aβ(1–40), and α-synuclein aggregates at a molar ratio of 1:10. In cell culture experiments, inclusion of recombinant 7B2, either in the medium of Neuro-2A cells or intracellularly via adenoviral 7B2 overexpression, blocked the neurocytotoxic effect of Aβ(1–42) and significantly increased cell viability. Conversely, knockdown of 7B2 by RNAi increased Aβ(1–42)-induced cytotoxicity. In the brains of APP/PSEN1 mice, a model of AD amyloidosis, immunoreactive 7B2 co-localized with aggregation-prone proteins and their respective aggregates. Furthermore, in the hippocampus and substantia nigra of human AD- and PD-affected brains, 7B2 was highly co-localized with Aβ plaques and α-synuclein deposits, strongly suggesting physiological association. Our data provide insight into novel functions of 7B2 and establish this neural protein as an anti-aggregation chaperone associated with neurodegenerative disease. |
format | Online Article Text |
id | pubmed-3542996 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-35429962013-01-14 The Neuroendocrine Protein 7B2 Suppresses the Aggregation of Neurodegenerative Disease-related Proteins Helwig, Michael Hoshino, Akina Berridge, Casey Lee, Sang-Nam Lorenzen, Nikolai Otzen, Daniel E. Eriksen, Jason L. Lindberg, Iris J Biol Chem Neurobiology Neurodegenerative diseases such as Alzheimer (AD) and Parkinson (PD) are characterized by abnormal aggregation of misfolded β-sheet-rich proteins, including amyloid-β (Aβ)-derived peptides and tau in AD and α-synuclein in PD. Correct folding and assembly of these proteins are controlled by ubiquitously expressed molecular chaperones; however, our understanding of neuron-specific chaperones and their involvement in the pathogenesis of neurodegenerative diseases is limited. We here describe novel chaperone-like functions for the secretory protein 7B2, which is widely expressed in neuronal and endocrine tissues. In in vitro experiments, 7B2 efficiently prevented fibrillation and formation of Aβ(1–42), Aβ(1–40), and α-synuclein aggregates at a molar ratio of 1:10. In cell culture experiments, inclusion of recombinant 7B2, either in the medium of Neuro-2A cells or intracellularly via adenoviral 7B2 overexpression, blocked the neurocytotoxic effect of Aβ(1–42) and significantly increased cell viability. Conversely, knockdown of 7B2 by RNAi increased Aβ(1–42)-induced cytotoxicity. In the brains of APP/PSEN1 mice, a model of AD amyloidosis, immunoreactive 7B2 co-localized with aggregation-prone proteins and their respective aggregates. Furthermore, in the hippocampus and substantia nigra of human AD- and PD-affected brains, 7B2 was highly co-localized with Aβ plaques and α-synuclein deposits, strongly suggesting physiological association. Our data provide insight into novel functions of 7B2 and establish this neural protein as an anti-aggregation chaperone associated with neurodegenerative disease. American Society for Biochemistry and Molecular Biology 2013-01-11 2012-11-21 /pmc/articles/PMC3542996/ /pubmed/23172224 http://dx.doi.org/10.1074/jbc.M112.417071 Text en © 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles |
spellingShingle | Neurobiology Helwig, Michael Hoshino, Akina Berridge, Casey Lee, Sang-Nam Lorenzen, Nikolai Otzen, Daniel E. Eriksen, Jason L. Lindberg, Iris The Neuroendocrine Protein 7B2 Suppresses the Aggregation of Neurodegenerative Disease-related Proteins |
title | The Neuroendocrine Protein 7B2 Suppresses the Aggregation of Neurodegenerative Disease-related Proteins |
title_full | The Neuroendocrine Protein 7B2 Suppresses the Aggregation of Neurodegenerative Disease-related Proteins |
title_fullStr | The Neuroendocrine Protein 7B2 Suppresses the Aggregation of Neurodegenerative Disease-related Proteins |
title_full_unstemmed | The Neuroendocrine Protein 7B2 Suppresses the Aggregation of Neurodegenerative Disease-related Proteins |
title_short | The Neuroendocrine Protein 7B2 Suppresses the Aggregation of Neurodegenerative Disease-related Proteins |
title_sort | neuroendocrine protein 7b2 suppresses the aggregation of neurodegenerative disease-related proteins |
topic | Neurobiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542996/ https://www.ncbi.nlm.nih.gov/pubmed/23172224 http://dx.doi.org/10.1074/jbc.M112.417071 |
work_keys_str_mv | AT helwigmichael theneuroendocrineprotein7b2suppressestheaggregationofneurodegenerativediseaserelatedproteins AT hoshinoakina theneuroendocrineprotein7b2suppressestheaggregationofneurodegenerativediseaserelatedproteins AT berridgecasey theneuroendocrineprotein7b2suppressestheaggregationofneurodegenerativediseaserelatedproteins AT leesangnam theneuroendocrineprotein7b2suppressestheaggregationofneurodegenerativediseaserelatedproteins AT lorenzennikolai theneuroendocrineprotein7b2suppressestheaggregationofneurodegenerativediseaserelatedproteins AT otzendaniele theneuroendocrineprotein7b2suppressestheaggregationofneurodegenerativediseaserelatedproteins AT eriksenjasonl theneuroendocrineprotein7b2suppressestheaggregationofneurodegenerativediseaserelatedproteins AT lindbergiris theneuroendocrineprotein7b2suppressestheaggregationofneurodegenerativediseaserelatedproteins AT helwigmichael neuroendocrineprotein7b2suppressestheaggregationofneurodegenerativediseaserelatedproteins AT hoshinoakina neuroendocrineprotein7b2suppressestheaggregationofneurodegenerativediseaserelatedproteins AT berridgecasey neuroendocrineprotein7b2suppressestheaggregationofneurodegenerativediseaserelatedproteins AT leesangnam neuroendocrineprotein7b2suppressestheaggregationofneurodegenerativediseaserelatedproteins AT lorenzennikolai neuroendocrineprotein7b2suppressestheaggregationofneurodegenerativediseaserelatedproteins AT otzendaniele neuroendocrineprotein7b2suppressestheaggregationofneurodegenerativediseaserelatedproteins AT eriksenjasonl neuroendocrineprotein7b2suppressestheaggregationofneurodegenerativediseaserelatedproteins AT lindbergiris neuroendocrineprotein7b2suppressestheaggregationofneurodegenerativediseaserelatedproteins |