Cancer and neurodegeneration: two sides, same coin?

Two papers just published would at first glance have little in common: one features a novel approach to combating metastases [1] whilst the other suggests a new strategy for treating Alzheimer’s, [2]. Nonetheless, here we describe a possible link based on the concept that both cancer and neurodegeneration are inappropriately activated forms of development, and in both cases could be mediated by the same bioactive peptide acting at the same receptor. A fundamental problem in animal biology is how the three major control processes of the body, the endocrine, immune, and central nervous systems, achieve the coordination that is essential for the cohesive functioning of the organism. When perturbed, such coordination could be a central, albeit overlooked, factor in the aetiology of many disease states from cancer to neurodegeneration. Acetylcholinesterase (AChE) has non-classical, non-enzymatic actions that could be pivotal in both brain development and degeneration, this latter process could be an aberrant recapitulation of the former by virtue of the effects of an AChE derived C-terminal peptide, acting at an allosteric site at the alpha-7 nictotinic acetylcholine receptor (α7-nAChR) [3]. Both the α7-nAChR and AChE are present early in embryonic tissues, well before the appearance of the choline acetyltransferase (ChAT) which is required for the synthesis of acetylcholine (ACh). Additionally, recent published papers show the different levels of AChE peptide in different stages of development [4], and in brain of Alzheimer’s disease patients [2], where development levels of peptides are recapitulated in AD brains. Both in vitro and ex vivo studies show actions of the AChEpeptide along a trophic-toxic spectrum, where neurotrophic effects occur in response to short, low doses of peptide treatment whereas longer exposure result in cell death [3]. Binding of peptide to an allosteric site on Editorial