Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer's disease

Research output: Contribution to journal › Journal article › Research › peer-review

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Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer's disease. / Fang, Evandro F; Hou, Yujun; Palikaras, Konstantinos; Adriaanse, Bryan A; Kerr, Jesse S; Yang, Beimeng; Lautrup, Sofie; Hasan-Olive, Md Mahdi; Caponio, Domenica; Dan, Xiuli; Rocktäschel, Paula; Croteau, Deborah L; Akbari, Mansour; Greig, Nigel H; Fladby, Tormod; Nilsen, Hilde; Cader, M Zameel; Mattson, Mark P; Tavernarakis, Nektarios; Bohr, Vilhelm A.

In: Nature Neuroscience, Vol. 22, 2019, p. 401-412.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Fang, EF, Hou, Y, Palikaras, K, Adriaanse, BA, Kerr, JS, Yang, B, Lautrup, S, Hasan-Olive, MM, Caponio, D, Dan, X, Rocktäschel, P, Croteau, DL, Akbari, M, Greig, NH, Fladby, T, Nilsen, H, Cader, MZ, Mattson, MP, Tavernarakis, N & Bohr, VA 2019, 'Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer's disease', Nature Neuroscience, vol. 22, pp. 401-412. https://doi.org/10.1038/s41593-018-0332-9

APA

Fang, E. F., Hou, Y., Palikaras, K., Adriaanse, B. A., Kerr, J. S., Yang, B., Lautrup, S., Hasan-Olive, M. M., Caponio, D., Dan, X., Rocktäschel, P., Croteau, D. L., Akbari, M., Greig, N. H., Fladby, T., Nilsen, H., Cader, M. Z., Mattson, M. P., Tavernarakis, N., & Bohr, V. A. (2019). Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer's disease. Nature Neuroscience, 22, 401-412. https://doi.org/10.1038/s41593-018-0332-9

Vancouver

Fang EF, Hou Y, Palikaras K, Adriaanse BA, Kerr JS, Yang B et al. Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer's disease. Nature Neuroscience. 2019;22:401-412. https://doi.org/10.1038/s41593-018-0332-9

Author

Fang, Evandro F ; Hou, Yujun ; Palikaras, Konstantinos ; Adriaanse, Bryan A ; Kerr, Jesse S ; Yang, Beimeng ; Lautrup, Sofie ; Hasan-Olive, Md Mahdi ; Caponio, Domenica ; Dan, Xiuli ; Rocktäschel, Paula ; Croteau, Deborah L ; Akbari, Mansour ; Greig, Nigel H ; Fladby, Tormod ; Nilsen, Hilde ; Cader, M Zameel ; Mattson, Mark P ; Tavernarakis, Nektarios ; Bohr, Vilhelm A. / Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer's disease. In: Nature Neuroscience. 2019 ; Vol. 22. pp. 401-412.

Bibtex

@article{a3f299aef2024dc39a92230629084974,
title = "Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer's disease",
abstract = "Accumulation of damaged mitochondria is a hallmark of aging and age-related neurodegeneration, including Alzheimer's disease (AD). The molecular mechanisms of impaired mitochondrial homeostasis in AD are being investigated. Here we provide evidence that mitophagy is impaired in the hippocampus of AD patients, in induced pluripotent stem cell-derived human AD neurons, and in animal AD models. In both amyloid-β (Aβ) and tau Caenorhabditis elegans models of AD, mitophagy stimulation (through NAD+ supplementation, urolithin A, and actinonin) reverses memory impairment through PINK-1 (PTEN-induced kinase-1)-, PDR-1 (Parkinson's disease-related-1; parkin)-, or DCT-1 (DAF-16/FOXO-controlled germline-tumor affecting-1)-dependent pathways. Mitophagy diminishes insoluble Aβ1-42 and Aβ1-40 and prevents cognitive impairment in an APP/PS1 mouse model through microglial phagocytosis of extracellular Aβ plaques and suppression of neuroinflammation. Mitophagy enhancement abolishes AD-related tau hyperphosphorylation in human neuronal cells and reverses memory impairment in transgenic tau nematodes and mice. Our findings suggest that impaired removal of defective mitochondria is a pivotal event in AD pathogenesis and that mitophagy represents a potential therapeutic intervention.",
author = "Fang, {Evandro F} and Yujun Hou and Konstantinos Palikaras and Adriaanse, {Bryan A} and Kerr, {Jesse S} and Beimeng Yang and Sofie Lautrup and Hasan-Olive, {Md Mahdi} and Domenica Caponio and Xiuli Dan and Paula Rockt{\"a}schel and Croteau, {Deborah L} and Mansour Akbari and Greig, {Nigel H} and Tormod Fladby and Hilde Nilsen and Cader, {M Zameel} and Mattson, {Mark P} and Nektarios Tavernarakis and Bohr, {Vilhelm A}",
year = "2019",
doi = "10.1038/s41593-018-0332-9",
language = "English",
volume = "22",
pages = "401--412",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer's disease

AU - Fang, Evandro F

AU - Hou, Yujun

AU - Palikaras, Konstantinos

AU - Adriaanse, Bryan A

AU - Kerr, Jesse S

AU - Yang, Beimeng

AU - Lautrup, Sofie

AU - Hasan-Olive, Md Mahdi

AU - Caponio, Domenica

AU - Dan, Xiuli

AU - Rocktäschel, Paula

AU - Croteau, Deborah L

AU - Akbari, Mansour

AU - Greig, Nigel H

AU - Fladby, Tormod

AU - Nilsen, Hilde

AU - Cader, M Zameel

AU - Mattson, Mark P

AU - Tavernarakis, Nektarios

AU - Bohr, Vilhelm A

PY - 2019

Y1 - 2019

N2 - Accumulation of damaged mitochondria is a hallmark of aging and age-related neurodegeneration, including Alzheimer's disease (AD). The molecular mechanisms of impaired mitochondrial homeostasis in AD are being investigated. Here we provide evidence that mitophagy is impaired in the hippocampus of AD patients, in induced pluripotent stem cell-derived human AD neurons, and in animal AD models. In both amyloid-β (Aβ) and tau Caenorhabditis elegans models of AD, mitophagy stimulation (through NAD+ supplementation, urolithin A, and actinonin) reverses memory impairment through PINK-1 (PTEN-induced kinase-1)-, PDR-1 (Parkinson's disease-related-1; parkin)-, or DCT-1 (DAF-16/FOXO-controlled germline-tumor affecting-1)-dependent pathways. Mitophagy diminishes insoluble Aβ1-42 and Aβ1-40 and prevents cognitive impairment in an APP/PS1 mouse model through microglial phagocytosis of extracellular Aβ plaques and suppression of neuroinflammation. Mitophagy enhancement abolishes AD-related tau hyperphosphorylation in human neuronal cells and reverses memory impairment in transgenic tau nematodes and mice. Our findings suggest that impaired removal of defective mitochondria is a pivotal event in AD pathogenesis and that mitophagy represents a potential therapeutic intervention.

AB - Accumulation of damaged mitochondria is a hallmark of aging and age-related neurodegeneration, including Alzheimer's disease (AD). The molecular mechanisms of impaired mitochondrial homeostasis in AD are being investigated. Here we provide evidence that mitophagy is impaired in the hippocampus of AD patients, in induced pluripotent stem cell-derived human AD neurons, and in animal AD models. In both amyloid-β (Aβ) and tau Caenorhabditis elegans models of AD, mitophagy stimulation (through NAD+ supplementation, urolithin A, and actinonin) reverses memory impairment through PINK-1 (PTEN-induced kinase-1)-, PDR-1 (Parkinson's disease-related-1; parkin)-, or DCT-1 (DAF-16/FOXO-controlled germline-tumor affecting-1)-dependent pathways. Mitophagy diminishes insoluble Aβ1-42 and Aβ1-40 and prevents cognitive impairment in an APP/PS1 mouse model through microglial phagocytosis of extracellular Aβ plaques and suppression of neuroinflammation. Mitophagy enhancement abolishes AD-related tau hyperphosphorylation in human neuronal cells and reverses memory impairment in transgenic tau nematodes and mice. Our findings suggest that impaired removal of defective mitochondria is a pivotal event in AD pathogenesis and that mitophagy represents a potential therapeutic intervention.

U2 - 10.1038/s41593-018-0332-9

DO - 10.1038/s41593-018-0332-9

M3 - Journal article

C2 - 30742114

VL - 22

SP - 401

EP - 412

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

ER -

ID: 213361371