Identification of soluble WSX-1 not as a dominant-negative but as an alternative functional subunit of a receptor for an anti-Alzheimer's disease rescue factor Humanin.
Hashimoto. Yuichi Y; Kurita. Megumi M; Matsuoka. Masaaki M
Key Findings
- Humanin helps prevent neuron death linked to Alzheimer’s disease.
- The known receptor complex includes CNTFR, full‑length WSX‑1, and gp130.
- A soluble, truncated WSX‑1 can replace full‑length WSX‑1 and still allow Humanin’s protective effect.
Practical Outcomes
- For now, this discovery is mostly scientific and doesn’t change how you would take Humanin. It does suggest that future supplements or drugs might target the soluble WSX‑1 pathway, but no new dosing or protocol advice is available yet.
Summary
Scientists found that a shorter version of a protein called WSX-1, which floats outside cells, can join with other proteins to form a receptor that lets the peptide Humanin protect brain cells from Alzheimer‑related damage. This shows Humanin can work through more than one receptor setup.
Abstract
Humanin (HN) inhibits Alzheimer's disease (AD)-relevant neuronal death and dysfunction, by interacting with a receptor (s) involving ciliary neurotrophic factor receptor alpha (CNTFR), WSX-1, and gp130. It remains unknown whether this complex is the sole HN receptor that mediates HN-induced anti-AD activity. We here report that an alternatively spliced WSX-1 isoform, encoding an extracellular 270-amino-acid region of WSX-1 with cytokine-binding regions (named soluble WSX-1; sWSX-1), is expressed in neuronal cells lacking function of full-length WSX-1 and enables HN to rescue AD-relevant death. This result suggests that CNTFR/soluble WSX-1/gp130 behaves as an alternative functional HN receptor.
Study Information
pubmed
2009
2009-08-22T00:00:00.000Z
10.1016/j.bbrc.2009.08.095
27
21