AsianScientist (Mar. 1, 2016) – Researchers have developed mitochondria-targeting nanoparticles that can effectively prevent neuronal cell death. Their study, published in ACS Nano, suggests that preventing oxidative stress in the mitochondria of the brain could be used to treat Alzheimer’s disease.
Alzheimer’s disease (AD) disrupts both the way electrical charges travel within cells and the activity of neurotransmitters. The major pathological indicators of AD are the accumulation of amyloid beta (Aβ) plaques and neurofibrillary tangles in the brain.
Over time, single molecules of Aβ cluster into plaques which block cell-to-cell signalling at synapses and activate the immune system. Neurofibrillary tangles, on the other hand, are formed when the tau protein required to maintain the transport networks of the cell break down. As a result, the brain cells die due to a lack of essential proteins and nutrients.
The plaques and tangles described above are currently the leading working theory explaining the cell death and tissue loss found in an AD brain, though the theory is yet to be irrefutably confirmed. The effects of AD on the brain, however, are well known: brain cells slowly disintegrate, the disease progressively invades different parts of the brain, creating unique changes that signal the various stages of Alzheimer’s.
In the present study, Professor Mook Inhee’s group at Seoul National University and researchers at the Center for Nanoparticle Research of the South Korea’s Institute for Basic Science (IBS) investigated whether antioxidants targeting the mitochondria could treat AD in a mouse model.
Brain cells are powered by mitochondria, tiny power plants within cells that produce the energy required for each cell to function. Reactive oxygen species (ROS) are formed as a natural by-product of normal metabolism of oxygen. However, abnormal generation of ROS resulting from mitochondrial dysfunction can lead to neuronal cell death. Additionally, Aβ-induced mitochondrial dysfunction also has been known to be a possible cause of AD through abnormal production of ROS.
To remove ROS in mice genetically modified to show symptoms of AD, the researchers used ceria (CeO2) nanoparticles, strong and recyclable ROS scavengers that shuttle between Ce3+ and Ce4+ oxidation states. The nanoparticles were targeted to the mitochondria using a compound called triphenylphosphonium.
The results showed that the mitochondria-localized ceria nanoparticles effectively suppressed neuronal death and restored neuronal viability of the AD-affected mouse.
Since the accumulation of Aβ did not differ significantly between the brains of the affected and non-treated mouse, the researchers concluded that the mitochondria-targeting ceria NPs ameliorated the neuronal damage of the test subject in an indirect way, independent of the Aβ accumulation.
“This study is quite remarkable in that the collaborative research between nano science and biomedical science has led to the development of a potent therapeutic agent against reactive oxygen species in the mitochondria, which is deemed to be one of major culprits in a number of diseases,” said Professor Hyeon Taeghwan, director of IBS.
The article can be found at: Kwon et al. (2016) Mitochondria-Targeting Ceria Nanoparticles as Antioxidants for Alzheimer’s Disease.
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Source: Institute for Basic Science.
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