We thank Dr. Zhu for citing our work (Iijima-Ando et al., 2009) in his comment. In our Aβ42 fly brain neurons, mitochondria were reduced in axons and dendrites, and accumulated in the somata without severe mitochondrial damage or neurodegeneration. At this stage, organization of microtubules and distribution of synaptic vesicle markers were not significantly altered, suggesting that mitochondrial mislocalization occurs without global axonal transport defects.
By knocking down milton, an adaptor protein that links mitochondria and kinesin, we showed that reduction in mitochondria transport exacerbated Aβ42-induced behavioral defects. Furthermore, milton knockdown by itself caused neuronal dysfunction at a later stage. Our results indicate that Aβ42-induced mitochondrial mislocalization contributes to Aβ42-induced neuronal dysfunction in vivo.
References:
Iijima-Ando K, Hearn SA, Shenton C, Gatt A, Zhao L, Iijima K.
Mitochondrial mislocalization underlies Abeta42-induced neuronal dysfunction in a Drosophila model of Alzheimer's disease.
PLoS One. 2009;4(12):e8310.
PubMed.
For mitochondrial effects in AD please see our Pharmacogenomics Journal article published in 2009. localizing a variable polyT mutation in the translocase of the outer mitochondrial membrane as a diagnostic predictor of risk for AD.
We thank all the commentators on our paper, "Expression of beta amyloid induced age-dependent presynaptic and axonal changes in Drosophila."
Our examination, through genetic manipulation, of the role of critical mitochondria fission and fusion genes in the mitochondrial abnormalities induced by Aβ expression will be finished soon.
Comments
Thomas Jefferson University
We thank Dr. Zhu for citing our work (Iijima-Ando et al., 2009) in his comment. In our Aβ42 fly brain neurons, mitochondria were reduced in axons and dendrites, and accumulated in the somata without severe mitochondrial damage or neurodegeneration. At this stage, organization of microtubules and distribution of synaptic vesicle markers were not significantly altered, suggesting that mitochondrial mislocalization occurs without global axonal transport defects.
By knocking down milton, an adaptor protein that links mitochondria and kinesin, we showed that reduction in mitochondria transport exacerbated Aβ42-induced behavioral defects. Furthermore, milton knockdown by itself caused neuronal dysfunction at a later stage. Our results indicate that Aβ42-induced mitochondrial mislocalization contributes to Aβ42-induced neuronal dysfunction in vivo.
References:
Iijima-Ando K, Hearn SA, Shenton C, Gatt A, Zhao L, Iijima K. Mitochondrial mislocalization underlies Abeta42-induced neuronal dysfunction in a Drosophila model of Alzheimer's disease. PLoS One. 2009;4(12):e8310. PubMed.
View all comments by Kanae AndoFormer Duke University Professor
For mitochondrial effects in AD please see our Pharmacogenomics Journal article published in 2009. localizing a variable polyT mutation in the translocase of the outer mitochondrial membrane as a diagnostic predictor of risk for AD.
View all comments by Allen RosesShanghai Advanced Research Institute, Chinese Academy of Sciences
We thank all the commentators on our paper, "Expression of beta amyloid induced age-dependent presynaptic and axonal changes in Drosophila."
Our examination, through genetic manipulation, of the role of critical mitochondria fission and fusion genes in the mitochondrial abnormalities induced by Aβ expression will be finished soon.
View all comments by Fu-De HuangMake a Comment
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