Acetylcholinesterase, read-through variant (AChE-R)

Acetylcholinesterase, read-through variant (AChE-R) is a splice variant of the enzyme acetylcholinesterase, produced by alternative splicing of the ACHE gene[1][3][4]. Unlike the canonical “synaptic” (AChE-S) form, AChE-R is monomeric, soluble, and is notably upregulated in conditions of cellular stress, during embryonic development, and in tumor cells[1][3]. AChE-R is also found in various tissues, including the brain, blood, and ovary, and possesses a unique C-terminal sequence conferring non-catalytic properties[3][4]. While its main classical function—hydrolyzing acetylcholine to terminate neurotransmission—is shared with other AChE isoforms, the read-through variant also exerts non-enzymatic trophic roles including regulation of cell proliferation, differentiation, apoptosis, and neurodevelopment[1][3][4]. Increased expression of AChE-R has been reported in Alzheimer’s disease brains, in certain cancers, and under stressful conditions[4][5]. Drugs that interact with acetylcholinesterase, including several approved Alzheimer’s disease therapeutics (e.g., donepezil, rivastigmine, galantamine, tacrine, and huperzine A), may also interact with AChE-R, primarily by inhibiting its catalytic activity but possibly affecting its non-classical functions as well[3][4]. The specific upregulation or inhibition of AChE-R may serve as a biomarker in certain disease contexts, notably Alzheimer’s disease[4]. Safety concerns with targeting acetylcholinesterase include risks of excessive cholinergic stimulation (which can lead to cholinergic crisis) and the possibility that altering AChE-R’s non-catalytic functions could unintentionally affect cell survival, development, or stress responses[1][4][5]. Overall, the human acetylcholinesterase, read-through variant is considered both an enzyme and a modulator of cell signaling, with significant implications in neurobiology, neurodegeneration, cancer, and stress physiology[3][4][5].

Other names

Readthrough acetylcholinesteraseAChE-R

Acetylcholinesterase inhibition (increases synaptic acetylcholine); Non-enzymatic modulation of cell signaling and apoptosis.