RT Journal Article
T1 Increased mitochondrial calcium levels associated with neuronal death in a mouse model of Alzheimer's disease
A1 Calvo-Rodriguez, Maria
A1 Hou, Steven S.
A1 Snyder, Austin C.
A1 Kharitonova, Elizabeth K.
A1 Russ, Alyssa N.
A1 Das, Sudeshna
A1 Fan, Zhanyun
A1 Muzikansky, Alona
A1 Garcia-Alloza, Monica
A1 Serrano-Pozo, Alberto
A1 Hudry, Eloise
A1 Bacskai, Brian J.
K1 Mitochondria
K1 Calcium
K1 Cell death
K1 Amyloid
K1 Brain
K1 Genes
K1 Microscopy
K1 Alzheimer disease
K1 Lead
K1 Mitocondrias
K1 Calcio
K1 Muerte celular
K1 Amiloide
K1 Encéfalo
K1 Microscopía
K1 Enfermedad de Alzheimer
K1 Plomo
AB Mitochondria contribute to shape intraneuronal Ca2+ signals. Excessive Ca2+ taken up by mitochondria could lead to cell death. Amyloid beta (Aβ) causes cytosolic Ca2+ overload, but the effects of Aβ on mitochondrial Ca2+ levels in Alzheimer's disease (AD) remain unclear. Using a ratiometric Ca2+ indicator targeted to neuronal mitochondria and intravital multiphoton microscopy, we find increased mitochondrial Ca2+ levels associated with plaque deposition and neuronal death in a transgenic mouse model of cerebral β-amyloidosis. Naturally secreted soluble Aβ applied onto the healthy brain increases Ca2+ 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 Ca2+ transporter genes, but upregulation in the genes related to mitochondrial Ca2+ efflux pathways, suggesting a counteracting effect to avoid Ca2+ overload. We propose lowering neuronal mitochondrial Ca2+ by inhibiting the mitochondrial Ca2+ uniporter as a novel potential therapeutic target against AD.
PB Springer Nature
YR 2020
FD 2020-05-01
LK http://hdl.handle.net/10668/3567
UL http://hdl.handle.net/10668/3567
LA en
NO Calvo-Rodriguez M, Hou SS, Snyder AC, Kharitonova EK, Russ AN, Das S, et al. Increased mitochondrial calcium levels associated with neuronal death in a mouse model of Alzheimer's disease. Nat Commun. 2020 May 1;11(1):2146.
DS RISalud
RD Apr 19, 2025