Modulators of Acetylcholinesterase Activity: From Alzheimer's Disease to Anti-Cancer Drugs

Abstract

It is not clear a patient treated for neurodegenerative condition prone to increased risk for some types of cancer and vice versa. This is necessary to keep in mind during rational drug design process for all therapies, which are based on AChE as a target molecule.

IGFBP-3 Blocks Hyaluronan-CD44 Signaling, Leading to Increased Acetylcholinesterase Levels in A549 Cell Media and Apoptosis in a p53-Dependent Manner

“…AChE, encoded by a single gene, is a member of the serine hydrolase family using a serine residue at the active site 62 . While AChE is well-known for its classical key role in the catalytic hydrolysis of cholinergic neurotransmitters, recent studies have shown non-classical functions of the enzyme as a potentially promising tumor growth suppresser and regulator of apoptosis 61 , suggesting that elevated AChE expression and/or activity in response to apoptotic stimuli could serve as a marker of apoptosis and promising anticancer therapeutic 63,64 . While cells overexpressing AChE undergo apoptosis more easily than controls, AChE is not thought to be an apoptosis initiator 64 .…”

“…While cells overexpressing AChE undergo apoptosis more easily than controls, AChE is not thought to be an apoptosis initiator 64 . Some tumor cells show no expression of AChE and are not sensitive to apoptosis induction suggesting that low levels of AChE protect the cells against apoptosis 61,63,64 .…”

Atividades Antioxidante, Anticolinesterasica E Citotóxica De Metabolitos De Fungos Endofiticos / Antioxidant, Anticolinesterasic and Cytoxic Activities of Endophytic Fungus Metabolites

“…Considerando que o solvente de acetato de etila consegue extrair componentes da classe fenólica, a atividade encontrada pode estar relacionada a estes compostos pois na literatura existe ampla discussão sobre a atividade antioxidante de compostos fenólicos como quinonas, taninos e flavonoides (ALVES et al, 2017;MARTINS et al, 2018;MORAIS et al, 2017;PENIDO et al, 2017;TOMIOTTO-PELLISSIER et al, 2018). Sabe-se que compostos inibidores da AChE aumentam os níveis de acetilcolina endógena e possivelmente são úteis no tratamento sintomático de atividades anticarcinogênicas, bem como potenciais para o tratamento de outras doenças do sistema nervoso com intensa produção de espécies reativas de oxigênio (como transtornos de ansiedade e doença de Alzheimer) (LAZAREVIC-PASTI et al, 2017).…”

Inhibition of acetylcholinesterase activity and β‑amyloid oligomer formation by 6‑bromotryptamine�A, a multi‑target anti‑Alzheimer's molecule

“…However, compared with the clinically used AChE inhibitors, such as donepezil (IC 50 on AChE activity, 12.3 nM) and galantamine (IC 50 on AChE activity, 410 nM), the AChE inhibition activity of 6-bromotryptamine A was not as potent (27). Several studies have reported that AChE is involved not only in neurotransmission, but also in the regulation of cell proliferation, differentiation and apoptosis (28), while overexpression of AChE was observed in numerous types of cancer (29,30). Notably, a number of AChE inhibitors are currently used or are under investigation for their potential application in cancer treatment.…”

“…For instance, donepezil has been reported to induce apoptosis of HL-60 human promyelocytic leukemia cells (31). Galantamine has also been proven to produce anti-proliferation effects against 3T3 cells (28). Similarly, certain approved chemotherapeutics have been demonstrated to inhibit AChE at their efficient anti-cancer concentrations.…”