Acetylcholinesterase read-through variant (AChE-R) (AChE-R)

Acetylcholinesterase read-through variant (AChE-R) is a soluble, monomeric isoform of the acetylcholinesterase enzyme produced through alternative splicing of the ACHE gene, specifically the retention of intron 4 (Soreq & Seidman, 2001). Unlike the primary synaptic variant (AChE-S), which is membrane-bound and terminates cholinergic signaling at synapses, AChE-R is typically induced by physical or psychological stress and is found in the cytoplasm and extracellular fluids (Evron et al., 2007). It plays a significant role in the body's response to stress, influencing neuronal plasticity and hematopoietic processes (Brenner et al., 2003). Pathologically, elevated levels of AChE-R are associated with neurodegenerative conditions like Alzheimer's disease and neuromuscular disorders such as Myasthenia Gravis (Soreq, 2015). Therapeutic strategies, most notably antisense oligonucleotides like Monarsen (EN101), have been developed to specifically target and reduce AChE-R expression to alleviate symptoms of these diseases (Sussman et al., 2003). By modulating the levels of this specific splice variant, researchers aim to restore cholinergic balance without disrupting the essential functions of the synaptic isoform.

Other names

AChE-RRead-through acetylcholinesteraseStress-induced acetylcholinesteraseAChE-readthrough

Antisense oligonucleotide-mediated knockdown of mRNA encoding the read-through variant (Evron et al., 2007)