| First Author | Calvo-Rodriguez M | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 2146 |
| PubMed ID | 32358564 | Mgi Jnum | J:291148 |
| Mgi Id | MGI:6444950 | Doi | 10.1038/s41467-020-16074-2 |
| Citation | Calvo-Rodriguez M, et al. (2020) Increased mitochondrial calcium levels associated with neuronal death in a mouse model of Alzheimer's disease. Nat Commun 11(1):2146 |
| abstractText | Mitochondria contribute to shape intraneuronal Ca(2+) signals. Excessive Ca(2+) taken up by mitochondria could lead to cell death. Amyloid beta (Abeta) causes cytosolic Ca(2+) overload, but the effects of Abeta on mitochondrial Ca(2+) levels in Alzheimer's disease (AD) remain unclear. Using a ratiometric Ca(2+) indicator targeted to neuronal mitochondria and intravital multiphoton microscopy, we find increased mitochondrial Ca(2+) levels associated with plaque deposition and neuronal death in a transgenic mouse model of cerebral beta-amyloidosis. Naturally secreted soluble Abeta applied onto the healthy brain increases Ca(2+) concentration in mitochondria, which is prevented by blockage of the mitochondrial calcium uniporter. RNA-sequencing from post-mortem AD human brains shows downregulation in the expression of mitochondrial influx Ca(2+) transporter genes, but upregulation in the genes related to mitochondrial Ca(2+) efflux pathways, suggesting a counteracting effect to avoid Ca(2+) overload. We propose lowering neuronal mitochondrial Ca(2+) by inhibiting the mitochondrial Ca(2+) uniporter as a novel potential therapeutic target against AD. |
