Study finds Plexin-B1 could be key to Alzheimer’s treatment, enhancing glial cell response

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Glial Cell,Allele,Gene

Researchers discovered that Plexin-B1 plays a crucial role in regulating peri-plaque glial nets in Alzheimer’s disease, potentially opening new avenues for treatment by targeting this protein.

By Tarun Sai LomteMay 29 2024Reviewed by Susha Cheriyedath, M.Sc. A recent study published in the journal Nature Neuroscience revealed that Plexin-B1, encoded by PLXNB1, regulates the activation of peri-plaque glial nets in Alzheimer’s disease .

Microglial phagocytic activity promotes plaque compaction, limiting the healthy neuron exposure to plaque. Furthermore, microglial coverage of plaques serves as a barrier limiting neurite exposure to neurotoxic protofibrillar Aβ hotspots. Amyloid plaques are also surrounded by reactive astrocytes. As such, the microglia and reactive astrocytes closely interact with Aβ and one another, forming peri-plaque glial nets.

A high density of Plxnb1 mRNA was observed in peri-plaque glial fibrillary acidic protein reactive astrocytes. Activated microglia around the plaque had scant Plxnb1 mRNA. Further, plexin-B1 expression was assessed using a Plxnb1 knockout allele containing a LacZ cassette before Plxnb1’s promoter and initial exons.

Related StoriesMoreover, plexin-B1 deletion reduced the number of peri-plaque microglia and the spacing of plaque-related microglia. Next, bulk RNA sequencing of the prefrontal cortex of mice with and without plexin-B1 was performed. This revealed over 2,700 genes with differential expression . Pathway analyses indicated that upregulated DEGs in mice without plexin-B1 were enriched for gene ontology terms associated with synaptic function and nervous system development.

 

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