| First Author | Hoshino A | Year | 2014 |
| Journal | J Neurochem | Volume | 128 |
| Issue | 3 | Pages | 419-30 |
| PubMed ID | 24102330 | Mgi Jnum | J:206615 |
| Mgi Id | MGI:5551558 | Doi | 10.1111/jnc.12454 |
| Citation | Hoshino A, et al. (2014) A novel function for proSAAS as an amyloid anti-aggregant in Alzheimer's disease. J Neurochem 128(3):419-30 |
| abstractText | Neurodegenerative diseases such as Alzheimer's disease (AD) are characterized by an abnormal aggregation of misfolded beta-sheet rich proteins such as beta-amyloid (Abeta). Various ubiquitously expressed molecular chaperones control the correct folding of cellular proteins and prevent the accumulation of harmful species. We here describe a novel anti-aggregant chaperone function for the neuroendocrine protein proSAAS, an abundant secretory polypeptide that is widely expressed within neural and endocrine tissues and which has previously been associated with neurodegenerative disease in various proteomics studies. In the brains of 12-month-old APdE9 mice, and in the cortex of a human AD-affected brain, proSAAS immunoreactivity was highly colocalized with amyloid pathology. Immunoreactive proSAAS co-immunoprecipitated with Abeta immunoreactivity in lysates from APdE9 mouse brains. In vitro, proSAAS efficiently prevented the fibrillation of Abeta(1-42) at molar ratios of 1 : 10, and this anti-aggregation effect was dose dependent. Structure-function studies showed that residues 97-180 were sufficient for the anti-aggregation function against Abeta. Finally, inclusion of recombinant proSAAS in the medium of Neuro2a cells, as well as lentiviral-mediated proSAAS over-expression, blocked the neurocytotoxic effect of Abeta(1-42) in Neuro2a cells. Taken together, our results suggest that proSAAS may play a role in Alzheimer's disease pathology. |
