| First Author | Lim YA | Year | 2012 |
| Journal | Biochim Biophys Acta | Volume | 1822 |
| Issue | 8 | Pages | 1247-57 |
| PubMed ID | 22542901 | Mgi Jnum | J:185139 |
| Mgi Id | MGI:5427524 | Doi | 10.1016/j.bbadis.2012.04.007 |
| Citation | Lim YA, et al. (2012) Role of hippocalcin in mediating Abeta toxicity. Biochim Biophys Acta 1822(8):1247-57 |
| abstractText | Alzheimer's disease (AD) is the most common cause of dementia, and amyloid-beta (Abeta) plaques and tau-containing tangles are its histopathological hallmark lesions. These do not occur at random; rather, the neurodegenerative process is stereotyped in that it is initiated in the entorhinal cortex and hippocampal formation. Interestingly, it is the latter brain area where the calcium-sensing enzyme hippocalcin is highly expressed. Because calcium deregulation is a well-established pathomechanism in AD, we aimed to address the putative role of hippocalcin in human AD brain and transgenic mouse models. We found that hippocalcin levels are increased in human AD brain and in Abeta plaque-forming APP23 transgenic mice compared to controls. To determine the role of hippocalcin in Abeta toxicity, we treated primary cultures derived from hippocalcin knockout (HC KO) mice with Abeta and found them to be more susceptible to Abeta toxicity than controls. Likewise, treatment with either thapsigargin or ionomycin, both known to deregulate intracellular calcium levels, caused an increased toxicity in hippocampal neurons from HC KO mice compared to wild-type. We found further that mitochondrial complex I activity increased from 3 to 6months in hippocampal mitochondria from wild-type and HC KO mice, but that the latter exhibited a significantly stronger aging phenotype than wild-type. Abeta treatment induced significant toxicity on hippocampal mitochondria from HC KO mice already at 3months of age, while wild-type mitochondria were spared. Our data suggest that hippocalcin has a neuroprotective role in AD, presenting it as a putative biomarker. |
