Professor Yimin Zou: The key mechanism of brain synapse degeneration in Alzheimer's disease

In brain diseases such as Alzheimer's, these synaptic connections that store our precious memories are known to collapse and disappear prematurely

Neurobiologists at the University of California San Diego (University of California San Diego) have now discovered the long-sought mechanism for maintaining glutamate synapses

Despite great efforts, drug discovery for the treatment of Alzheimer's disease has been unsuccessful

The findings of this study were published in the journal Science Advances on August 18.

Glutamate synapses are highly polarized structures.

They were curious about whether these components are related to synaptic degeneration, and tested whether amyloid, a key driver of synapse loss in Alzheimer's disease, affects the function or interaction of these proteins

"It's like beta amyloid discovered the Achilles heel of our synapses long ago," Professor Zou said

When the researchers removed Vangl2 from neurons, they found that whether in neuron culture or in animals exposed to amyloid oligomers, beta amyloid no longer caused synaptic degradation

To further verify the hypothesis that this basic signaling pathway is the main target of synaptic degeneration in Alzheimer's disease, the researchers used 5XFAD mice, a well-known β-amyloid pathological mouse model

These exciting results indicate that the PCP pathway is the direct target of amyloid-induced synaptic loss in Alzheimer's disease

"Amyloid pathology and synapse loss usually occur in the early stages of Alzheimer's disease.

The neuroinflammation reflected by the activation of astrocytes and microglia is also a pathological feature of Alzheimer's disease.

"This finding may be applicable to general synaptic degeneration, because the PCP component may be the direct synaptic loss that mediates other neurodegenerative diseases (such as Parkinson's disease and Lou Gehrig's disease).

Journal Reference :

1. Bo Feng, Andiara E.