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

Authors
 Michael Helwig ; Akina Hoshino ; Iris Lindberg ; Jason L. Eriksen ; Daniel E. Otzen‖ ; Nikolai Lorenzen‖ ; Sang-Nam Lee ; Casey Berridge 
Citation
 Journal of Biological Chemistry, Vol.288(2) : 1114~1124, 2013 
Journal Title
 Journal of Biological Chemistry 
ISSN
 0021-9258 
Issue Date
2013
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.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/86314
DOI
10.1074/jbc.M112.417071
Appears in Collections:
1. 연구논문 > 5. Research Institutes > 생체방어연구센터
Yonsei Authors
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