Summary: Researchers have identified a novel therapeutic target for Alzheimer’s disease by focusing on astrocytes, non-neuronal head tissues involved in waste removal. They found that astrocytic autophagy clears amyloid-beta ( Aβ ) oligomers, toxic proteins in Alzheimer’s patients, and helps restore cognitive functions.
This finding shifts the focus away from Alzheimer’s disease to astrocytes and opens up new avenues for drug development aimed at boosting apoptosis in these brain cells. The research represents a promising step in the development of treatments that stop or slow the development of Alzheimer’s disease.
Important Information:
- Astrocytes may reduce amyloid-beta formation and recover cognitive functions.
- Autophagy-associated chromosomes in astrocytes help rebuild damaged cells in Alzheimer’s.
- This study opens new pathways for Alzheimer’s care, targeting non-neuronal cells.
Origin: KIST
A research team led by Dr. Hoon Ryu from 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 from Boston University Chobanian &, Avedisian School of Medicine, has uncovered a new mechanism involving astrocytes for treating Alzheimer’s disease ( AD ) and proposed a novel therapeutic target.
In this study, the researchers revealed that autophagy pathway in astrocytes ( non-neuronal cells in the brain ) removes amyloid-beta ( Aβ ) oligomers, the toxic proteins found in the brains of AD patients, and recovers memory and cognitive functions.
Advertising, a representative type of senile memory, occurs when toxic proteins like Aβ, excessively aggregate and collect in the mind, leading to irritation and damage to neurons, causing the neurological disorders. The precise system for astrocytes to remove toxic proteins from around neurons is still a mystery, despite the medical community’s much interest in its role.
In order to maintain homeostasis, cells undergo apoptosis, in which they degrade and discard their individual components. The study team examined the ubiquitin procedure in astrocytes and discovered that astrocytes respond by inducing autophagy-related genes when dangerous protein buildup or disease is present in AD patients ‘ brains.
The researchers observed the healing of damaged cells by particularly injecting these autophagy-associated genes into astrocytes in Advertising mouse versions.
This study demonstrated that astrocytic autophagy improves memory and cognitive functions by reducing A-aggregates ( protein clumps ). Importantly, when autophagy-associated chromosomes were expressed in astrocytes of the brain, a mental place responsible for memory, the neuropathological indications were decreased.
Most importantly, this research demonstrated that the autophagy ductility of astrocytes is responsible for the elimination of A oligomers, a significant contributor to AD disease, thereby creating a novel potential therapeutic treatment option.
This research is particularly significant because it deviates from the traditional neuron-centered approach to developing AD drugs and instead views astrocytes ( non-neuronal cells ) as a novel therapeutic target.
The study team intends to conduct preliminary studies in the near future, as well as to further investigate drug developments that can increase the autophagic functionality of astrocytes to prevent or lessen dementia symptoms.
Dr. Ryu and Dr. Suhyun Kim ( the first author ) commented,” Our findings show that astrocytic autophagy restores neuronal damage and cognitive functions in the dementia brain.
We hope that this study will help us understand how biological mechanisms relate to autophagy and help us with future research on astrocyte waste elimination and mental health maintenance.
Funding: This research was supported by the Ministry of Science and ICT ( Minister Sang Im Yoo ), under KIST’s Major Projects and the Mid-career Researcher Support Program ( 2022R1A2C3013138 ), and the Ministry of Health and Welfare ( Minister Gyu-Hong Cho ), under the Dementia Overcoming Program ( RS-2023-KH137130 ).  ,
About this Alzheimer’s disease study information
Author: Ryu Hoon
Source: KIST
Contact: Ryu Hoon – KIST
Image: The image is credited to Neuroscience News
Original Research: Start exposure.
Hoon Ryu and colleagues ‘ study,” Astrocytic autophagy flexibility modulates A clearance and cognitivefunction in Alzheimer’s condition.” Chemical Aging
Abstract
Astrocytic apoptosis flexibility modulates Aβ clearing and cognitivefunction in Alzheimer’s illness
Background
Astrocytes, one of the most resilient cells in the brain, transform into reactive astrocytes in response to toxic proteins such as amyloid beta ( Aβ ) in Alzheimer’s disease ( AD ). But, aggressive astrocyte-mediated non-cell automatic neuropathological system is not fully understood however.
We wanted to find out whether A-induced proteotoxic tension affects the appearance of lysosomal genes and the control of autophagic flow in astrocytes, and if so, how A-induced autophagy-associated genes are involved in A certification in astrocytes of an animal model of AD.
Methods
In a time-dependent manner, whole RNA sequencing ( RNA-seq ) was used to identify gene expression patterns in A-treated human astrocytes. To verify the role of astrocytic autophagy in an AD mouse model, we developed AAVs expressing shRNAs for , MAP1LC3B/LC3B (LC3B )  , and , Sequestosome1 , ( SQSTM1 )  , based on AAV-R-CREon vector, which is a Cre recombinase-dependent gene-silencing system. Also, the effect of astrocyte-specific overexpression of LC3B on the neuropathology in AD ( APP/PS1 ) mice was determined.
Using confocal microscope and the transmission electron microscope ( TEM), we were able to observe neuropathological changes in AD mice with astrocytic phagocytosis function. No novel object recognition tests ( NOR ) and no novel object place recognition tests ( NOPR ) were used to examine mice’s behavioral changes.
Results
Below, we show that astrocytes, unlike cells, undergo cheap shifts in autophagic methods to reduce Aβ. Aβ transiently induces appearance of , LC3B , dna and turns on a continuous translation of , SQSTM1 , dna. The nitrogen cycle and putrescine degradation pathway are both accelerated by the A-induced astrocytic autophagy. Moreover, astrocytes experience mitochondrial function and oxidative stress when phagocytosis is inhibited pathologically.
Astrocyte-specific knockout of , LC3B , and , SQSTM1 , substantially increases Aβ memorial development and GFAP-positive astrocytes in APP/PS1 animals, along with a considerable reduction of cerebral symbol and mental performance.
In contrast, astrocyte-specific expression of LC3B reduced Aβ particles in the head of APP/PS1 animals. In Advertising people, astrocytes from the brain exhibit an increase in LC3B and SQSTM1 proteins.
Conclusions
Our data along show that A-induced astrocytic autophagic flexibility is a crucial cellular event that affects AD mice’s ability to maintain cognitive function and control A-induced A.
