Figures & data
Figure 1 Schematic representation of AChE-R role and mechanism of action and its interferences by antisense treatment. (A) AChE inhibition leads to the overstimulation of AChRs, with the subsequent induction of AChE-R pre mRNA. The rise of soluble AChE-R enhances ACh hydrolysis. This results in muscle weakness due to reduced cholinergic transmission to muscles, and induction of neuromuscular pathology. (B) 2-O-Met-Antisense treatment induces degradation of AChE-R mRNA, with an efficient reduction of the levels of AChE-R.
Notes: ACh is hydrolyzed by AChE-S, but, without saturation of the synaptic cleft with AChE-R, a greater number of ACh molecules remain in the cleft and AChR is activated. Increased levels of ACh prevail on the muscle weakening and pro-inflammatory effect of AChE-R. AChE-R neuromuscular pathology is ameliorated. Copyright © 2006, Wiley. Adapted with permission from Dori A, Soreq H. Neuromuscular therapeutics by RNA-targeted suppression of ACHE gene expression. Ann N Y Acad Sci. 2006;1082:77–90.Citation17
Abbreviations: ACh, acetylcholine; AChE, acetylcholinesterase; AChE-R, rare “read-through” isoform of AChE; AChE-S, synaptic isoform of AChE; nAChR, nicotinic acetylcholine receptor.
Abbreviations: ACh, acetylcholine; AChE, acetylcholinesterase; AChE-R, rare “read-through” isoform of AChE; AChE-S, synaptic isoform of AChE; nAChR, nicotinic acetylcholine receptor.
