Role of hippocalcin in mediating Aβ toxicity

Lim, Yun-An, Giese, Maria, Shepherd, Claire, Halliday, Glenda, Kobayashi, Masaaki, Takamatsu, Ken, Staufenbiel, Matthias, Eckert, Anne and Gotz, Jürgen (2012) Role of hippocalcin in mediating Aβ toxicity. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1822 8: 1247-1257. doi:10.1016/j.bbadis.2012.04.007


Author Lim, Yun-An
Giese, Maria
Shepherd, Claire
Halliday, Glenda
Kobayashi, Masaaki
Takamatsu, Ken
Staufenbiel, Matthias
Eckert, Anne
Gotz, Jürgen
Title Role of hippocalcin in mediating Aβ toxicity
Journal name Biochimica et Biophysica Acta - Molecular Basis of Disease   Check publisher's open access policy
ISSN 0925-4439
Publication date 2012-01-01
Year available 2012
Sub-type Article (original research)
DOI 10.1016/j.bbadis.2012.04.007
Open Access Status Not Open Access
Volume 1822
Issue 8
Start page 1247
End page 1257
Total pages 11
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Language eng
Abstract Alzheimer's disease (AD) is the most common cause of dementia, and amyloid-β (Aβ) 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 Aβ plaque-forming APP23 transgenic mice compared to controls. To determine the role of hippocalcin in Aβ toxicity, we treated primary cultures derived from hippocalcin knockout (HC KO) mice with Aβ and found them to be more susceptible to Aβ 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 6. months in hippocampal mitochondria from wild-type and HC KO mice, but that the latter exhibited a significantly stronger aging phenotype than wild-type. Aβ treatment induced significant toxicity on hippocampal mitochondria from HC KO mice already at 3. months 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.
Keyword Alzheimer
Amyloid
Calcium
Pathogenesis
Toxicity
Transgenic mice
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 31000_122572
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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