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The neuroendocrine peptide 7B2 prevents neurodegenerative disease‐related protein aggregation
Author(s) -
Helwig Michael,
Hoshino Akina,
Lee Sang-Nam,
Lorenzen Nikolai,
Otzen Daniel Erik,
Lindberg Iris
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.752.6
Subject(s) - substantia nigra , biology , protein aggregation , alpha synuclein , microbiology and biotechnology , synuclein , protein folding , chaperone (clinical) , neurodegeneration , parkinson's disease , disease , medicine , pathology
Neurodegenerative diseases like Alzheimer's (AD) and Parkinson's (PD) are characterized by an abnormal aggregation of misfolded beta‐sheet rich proteins such as β‐amyloid (Aβ), tau (in AD) and α‐synuclein (in PD). In healthy cells, the correct folding of proteins is controlled by ubiquitously expressed molecular chaperones, which prevent the accumulation of harmful protein species. Our understanding of this quality control machinery and its involvement in the pathogenesis of neurodegenerative diseases is, however, very limited. We here describe a novel chaperone‐like function for the neuroendocrine protein 7B2, a highly conserved protein that is widely expressed in the nervous and endocrine systems. In vitro , 7B2 efficiently prevented the fibrillation of Aβ(1–42), Aβ(1–40), tau and α‐synuclein at a molar ratio of 1:10. This anti‐aggregation effect was dose‐dependent and most effective when 7B2 was present as the full‐length (27 kDa) form. Both exogenous application of 7B2 into the medium of Neuro2A cells, as well as endogenous adenoviral‐mediated overexpression of 7B2 blocked the neurocytotoxic effect of Aβ(1–42) and significantly increased cell viability. In the substantia nigra of a human PD‐affected brain, 7B2 was highly colocalized with α‐synuclein, indicating a physiological association. Taken together our results suggest that 7B2 may play a role in the etiology of neurodegenerative diseases.