Abstract
β2M shuttle hypothesis in the dialysis related amyloidosis (DRA)
Highlights
We had showed “smoking gun” evidence that heparin could provoke the C-terminal unfolding in native β2M at clinical doses in HD setting, demonstrating causative implication of interstitial GAG molecules in the C-terminal unfolding of β2M because heparin is one of main GAG molecules as matrix substance in the interstitial space [8]
Our study imply that amyloid protein must be formed in extravascular space and cannot transfer crossing vascular wall, and more importantly, cannot be cleared via the kidney or even dialysis
We believe that the presence of intermediate β2microglobulin (I-β2M) with the unfolded C-terminal is “sine qua non” in development of the dialysis related amyloidosis (DRA), because a C-terminal unfolding could be confirmed in the natural A-β2M, i.e, D76Nβ2M [8,13]
Summary
As for molecular structure, I-β2M consists of species with partially unfolded C-terminal, which can refold reversibly to N-β2M. I’-β2M is supposed to consist of species with more, but not completely, unfolded C-terminal, which might be unlikely to refold to N-β2M. We had confirmed that the C-terminal of ⊿N6β2M was completely unfolded as same as 92/99β2M [7].
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