New insights into astrocytes offer hope for Alzheimer’s treatment

A research team 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, have discovered a novel mechanism involving astrocytes in the treatment of Alzheimer’s disease (AD) and proposed a new therapeutic target. In this study, researchers revealed that the autophagy pathway in astrocytes (non-neuronal cells in the brain) removes amyloid-beta (Aβ) oligomers, the toxic proteins found in the brains of Alzheimer’s patients, and impairs memory and cognitive function. functions restored.

AD, a representative form of senile dementia, occurs when toxic proteins such as Aβ abnormally aggregate and accumulate in the brain, leading to inflammation and damage to neurons, causing 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 own components to maintain homeostasis. The research team scrutinized the autophagy process in astrocytes and found that when toxic proteins accumulate 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 AD mouse models, the researchers observed the repair of damaged neurons.

This study showed that astrocytic autophagy reduces Aβ aggregates (protein clumps) and improves memory and cognitive functions. Notably, when autophagy-associated genes were expressed in astrocytes of the hippocampus, a brain region responsible for memory, neuropathological symptoms decreased. Most importantly, this study demonstrated that the autophagy plasticity of astrocytes is involved in eliminating Aβ oligomers, a major cause of AD pathology, thus presenting a new potential therapeutic avenue for the treatment of AD.

This research is particularly meaningful because it deviates from the traditional neuron-targeted approach to drug development for Alzheimer’s disease and instead identifies astrocytes (non-neuronal cells) as a novel target for therapy. The research team plans to further explore drug developments that can improve the autophagic function of astrocytes to prevent or alleviate dementia symptoms, and to conduct preclinical studies in the near future.

Dr. Ryu and Dr. Suhyun Kim (the first author) commented: “Our findings demonstrate that astrocytic autophagy restores neuronal damage and cognitive functions in the dementia brain. We hope that this study will advance our understanding of cellular mechanisms related to autophagy and contribute to future research on astrocyte waste removal and the maintenance of brain health.”