Alzheimer's Discovery Reveals "Achilles' Heel" of Synapse Degeneration
upstart writes:
Alzheimer's discovery reveals "Achilles' heel" of synapse degeneration:
Scientists believe one of the key culprits behind the cognitive decline seen in Alzheimer's are amyloid beta proteins that clump together and disrupt the brain's synaptic connections, but how they carry out such degeneration has remained unclear. A new study has shone compelling new light on this phenomenon, with the authors demonstrating how these toxic agents take aim at the "Achilles' heel" of synapses, and better yet, how they might just be stopped.
[...] Neurobiologists at the University of California (UC) San Diego focused on a major type of synapse called glutamatergic synapses. During brain development, these synapses are pieced together by a powerful signaling pathway called the planar cell polarity (PCP) pathway, which includes signaling components called Celsr3 and Vangl2. These work in harmony to stabilize and disassemble synapses, respectively, to keep their numbers at a healthy level.
[...] The researchers then turned their attention to another key component of the PCP pathway called Ryk, which functions much like Vangl2 in mediating synapse disassembly. Using special antibodies, the scientists blocked the function of Ryk and found that this too prevented the degeneration of synapses by the amyloid beta proteins. In mouse models of Alzheimer's, both knocking out the gene for Ryk and administering the Ryk-blocking antibody protected the synapses and preserved cognitive function.
"As amyloid beta pathology and synapse loss usually occurs in early stages of Alzheimer's disease, even before cognitive decline can be detected, early intervention, such as restoring the rebalance of the PCP pathway, will likely be beneficial for Alzheimer's patients," says Zou.
The Ryk antibody also proved effective at quelling some of the signs of neuroinflammation seen in Alzheimer's, though the exact mechanisms behind this are unclear. In any case, the scientists believe these results indicate the PCP could prove a valuable target in efforts to protect synapse loss in Alzheimer's disease, and potentially other conditions.
Also at: UC San Diego
Journal Reference:
Bo Feng, Andiara E. Freitas, Lilach Gorodetski, et al. Planar cell polarity signaling components are a direct target of -amyloid-associated degeneration of glutamatergic synapses [open], Science Advances (DOI: 10.1126/sciadv.abh2307)
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