Summary: Researchers have identified a new way to potentially slow or stop the progression of Alzheimer’s disease by targeting the plexin-B1 protein. Their study shows how reactive astrocytes and plexin-B1 play a crucial role in the elimination of amyloid plaques. This discovery opens new avenues for treatments of Alzheimer’s disease and highlights the importance of cellular interactions.
Highlights:
- Key protein: Targeting the plexin-B1 protein may improve the brain’s ability to clear amyloid plaques.
- Cellular interactions: Reactive astrocytes help control the removal of harmful deposits in the brain.
- Innovative treatments: The study opens new avenues for developing treatments against Alzheimer’s disease.
Source: Mount Sinai Hospital
Researchers at the Icahn School of Medicine at Mount Sinai have made a significant advance in Alzheimer’s disease research by identifying a new way to potentially slow or even stop the progression of the disease.
The study, which focuses on the role of reactive astrocytes and the protein plexin-B1 in the pathophysiology of Alzheimer’s disease, provides crucial information on communication between brain cells and opens the door to treatment strategies innovative.
It was published in Natural neuroscience on May 27.
This groundbreaking work focuses on manipulating the protein plexin-B1 to improve the brain’s ability to clear amyloid plaques, a hallmark of Alzheimer’s disease. Reactive astrocytes, a type of brain cell that activates in response to injury or disease, play a crucial role in this process.
They help control the spacing around amyloid plaques, thereby affecting how other brain cells can access and remove these harmful deposits.
“Our findings provide a promising avenue for developing new treatments by improving how cells interact with these harmful plaques,” said Roland Friedel, PhD, associate professor of neuroscience and neurosurgery at Icahn Mount Sinai and senior author of the study. study.
The research was driven by the analysis of complex data comparing healthy individuals to those with Alzheimer’s disease, with the aim of understanding the molecular and cellular underpinnings of the disease.
Hongyan Zou, PhD, professor of neurosurgery and neuroscience at Icahn Mount Sinai and one of the lead authors of the study, highlighted the broader implications of their findings: “Our study opens new avenues for disease research of Alzheimer’s, emphasizing the importance of cellular interactions in development. treatments of neurodegenerative diseases.
One of the most important achievements of the study is the validation of multi-scale genetic network models of Alzheimer’s disease.
“This study not only confirms one of the most important predictions of our genetic network models, but it also significantly advances our understanding of Alzheimer’s disease. This lays a strong foundation for developing new therapies targeting such highly predictive network models,” said Bin Zhang, PhD, Willard TC Johnson Research Professor of Neurogenetics at Icahn Mount Sinai and one of the study’s senior authors. .
By demonstrating the critical role of plexin-B1 in Alzheimer’s disease, the research highlights the potential of targeted therapies to disrupt disease progression.
The research team emphasizes that while their findings mark a significant advance in the fight against Alzheimer’s disease, additional research is needed to translate these findings into treatments for human patients.
“Our ultimate goal is to develop treatments that can prevent or slow the progression of Alzheimer’s disease,” added Dr. Zhang, emphasizing the team’s commitment to further exploring the therapeutic potential of plexin-B1 .
Funding: This study is supported by NIH National Institute on Aging (NIA) Grants U01AG046170 and RF1AG057440 and is part of the Target Discovery and Preclinical Validation Program led by the NIA Accelerating Medicines Partnership – Alzheimer’s Disease (AMP-AD).
This public-private partnership aims to shorten the time between the discovery of potential drug targets and the development of new drugs for the treatment and prevention of Alzheimer’s disease.
About this Alzheimer’s disease research news
Author: Jennifer Gutiérrez
Source: Mount Sinai Hospital
Contact: Jennifer Gutierrez – Mount Sinai Hospital
Picture: Image is credited to Neuroscience News
Original research: Closed access.
“Regulation of cell distance in peri-plaque glial networks by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease” by Roland Friedel et al. Natural neuroscience
Abstract
Regulation of cell distance in peri-plaque glial networks by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease
Communication between glial cells has a profound impact on the pathophysiology of Alzheimer’s disease (AD). Here we reveal that reactive astrocytes control the distance between cells in peri-plaque glial networks, which restricts microglia’s access to amyloid deposits.
This process is governed by the guidance receptor Plexin-B1 (PLXNB1), a core network gene in individuals with late-onset AD that is upregulated in plaque-associated astrocytes.
Deletion of plexin-B1 in a mouse model of AD resulted in reduced numbers of reactive astrocytes and microglia in peri-plaque glial networks, but higher coverage of plaques by glial processes, as well as transcriptional changes signifying reduced neuroinflammation.
Additionally, reduced footprint of glial networks was associated with lower overall plaque burden, a shift toward dense core-like plaques, and reduced neuritic dystrophy.
Overall, our study demonstrates that plexin-B1 regulates peri-plaque glial network activation in AD.
Relaxation of glial spacing by targeting homing receptors may present an alternative strategy to increase plaque compaction and reduce neuroinflammation in AD.
News Source : neurosciencenews.com
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