New research shows that astrocytes can remove the Alzheimer’s-associated beta-amyloid protein via autophagy, opening a promising new direction for therapeutic strategies focused on these brain cells.
The role of astrocytes in neurodegeneration leading to Alzheimer’s disease
An international research team has identified a new mechanism involving astrocytes for the treatment of Alzheimer’s disease (AD) and proposed a new therapeutic target. In their study, the researchers revealed that the autophagy pathway in astrocytes (non-neuronal cells in the brain) removes amyloid beta (Aβ) oligomers, toxic proteins present in the brains of AD patients, and recovers memory and cognitive functions.
The research, led by Dr. Hoon Ryu of the Korea Institute of Science and Technology (KIST, President Sang-Rok Oh) Brain Disease Research Group, in collaboration with Director Justin C. Lee of the Institute for Basic Science (IBS, President Do -Young Noh) and Professor Junghee Lee of Boston University Chobanian & Avedisian School of Medicine, was published in the journal Molecular Neurodegeneration.
THE’Alzheimer’sa representative form of senile dementia, occurs when toxic proteins, such as Aβ, aggregate and accumulate abnormally in the brain, causing inflammation and damage to neurons, leading to neurodegenerative disorders. Although the scientific community has long focused on the role of astrocytes in removing toxic proteins around neurons, the exact mechanism remains unclear.
Autophagy is a process by which cells break down and recycle their components to maintain homeostasis. The research team carefully examined the process of autophagy in astrocytes and found that when toxic protein accumulation or inflammation occurs in the brains of AD patients, astrocytes respond by inducing genes that regulate autophagy.
By delivering these autophagy-associated genes specifically into astrocytes in Alzheimer’s mouse models, the researchers observed recovery of damaged neurons.
This study demonstrated that astrocyte autophagy reduces Aβ aggregates (protein aggregates) and improves memory and cognitive functions. Specifically, when autophagy-associated genes were expressed in astrocytes of the hippocampus, a brain region responsible for memory, neuropathological symptoms decreased.
Even more significantly, this study demonstrated that astrocyte autophagy plasticity is involved in the clearance of Aβ oligomers, a major cause of Alzheimer’s pathology, thus presenting a new potential therapeutic avenue for the treatment of AD.
This research is particularly significant as it moves away from the traditional neuron-focused approach in Alzheimer’s drug development, instead identifying astrocytes (non-neuronal cells) as a new target for therapy. The research team plans to further explore drug developments that can enhance the autophagic function of astrocytes to prevent or alleviate dementia symptoms and conduct preclinical studies in the near future.
The Dr. Ryu and Dr. Suhyun Kim (the first author) commented: “Our results show that astrocytic autophagy restores neuronal damage and cognitive functions in the dementia brain. We hope that this study advances our understanding of cellular mechanisms related to autophagy and contributes to future research on waste removal by astrocytes and maintaining brain health.”
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