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Comment
. 2014 Sep 23;111(38):13680-1.
doi: 10.1073/pnas.1414554111. Epub 2014 Sep 9.

Toward a unified therapeutics approach targeting putative amyloid-β oligomer receptors

Cassia R Overk  1 , Eliezer Masliah  2
Affiliations
Comment

Toward a unified therapeutics approach targeting putative amyloid-β oligomer receptors

Cassia R Overk et al. Proc Natl Acad Sci U S A. .
No abstract available

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Putative Aβ oligomer receptors, signaling pathways, and therapeutic targets. A number of potential cell surface molecules (insulin receptor, NGF receptor, PrPc, mGluR5, EphA4, EphB2, NMDA, and Flizzed) that mediate the synaptotoxic effects of Aβ oligomers have been identified. In general terms, they can be divided into those that signal via tyrosine kinase (tyr k, fyn, and c-Abl) and those that hyperactivate CDK5/glycogen synthase kinase (GSK)3β. Therapeutics for AD might involve (1) directly clearing Aβ oligomers, (2) blocking the surface receptors, (3) interfering with signaling pathways, or (4) decreasing downstream effectors such as Tau. The study by Fu et al. identifies rhynchophylline (Rhy) as an antagonist of EphA4. The mechanisms as to how this compound protects neurons from the toxic effects of Aβ are unclear; however, Rhy might directly block EphA4 or interfere with signaling.
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