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The Neuroendocrine Protein 7B2 Suppresses the Aggregation of Neurodegenerative Disease-related Proteins

Authors
 Michael Helwig  ;  Akina Hoshino  ;  Casey Berridge  ;  Sang-Nam Lee  ;  Nikolai Lorenzen‖  ;  Daniel E. Otzen‖  ;  Jason L. Eriksen  ;  Iris Lindberg 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.288(2) : 1114-1124, 2013 
Journal Title
 JOURNAL OF BIOLOGICAL CHEMISTRY 
ISSN
 0021-9258 
Issue Date
2013
MeSH
Aged ; Amino Acid Sequence ; Amyloid beta-Peptides/antagonists & inhibitors* ; Amyloid beta-Peptides/metabolism ; Animals ; Cell Death/physiology ; Female ; Hippocampus/metabolism ; Humans ; Immunohistochemistry ; Mice ; Mice, Transgenic ; Microscopy, Electron, Transmission ; Molecular Sequence Data ; Neurodegenerative Diseases/metabolism* ; Neuroendocrine Secretory Protein 7B2/chemistry ; Neuroendocrine Secretory Protein 7B2/metabolism ; Neuroendocrine Secretory Protein 7B2/physiology* ; Substantia Nigra/metabolism ; alpha-Synuclein/antagonists & inhibitors* ; alpha-Synuclein/metabolism
Keywords
Aggregation ; Amyloid ; Chaperone Chaperonin ; Neurodegeneration ; Neurodegenerative Diseases ; Protein Aggregation ; 7B2 ; Alzheimer ; Parkinson
Abstract
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.
Files in This Item:
T201300283.pdf Download
DOI
10.1074/jbc.M112.417071
Appears in Collections:
5. Research Institutes (연구소) > Research Center for Human Natural Defense System (생체방어연구센터) > 1. Journal Papers
Yonsei Authors
Lee, Sang Nam(이상남)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/86314
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