A review article in the frame of PHOTOTHERAPORT project has been recently published shedding new light on the cholinergic system. The article, titled «Light-Activated Pharmacological Tools for Exploring the Cholinergic System», highlights how photopharmacology is reshaping the landscape of neurological drug research.
The cholinergic system, which plays essential roles in cognitive function, neuromuscular activity, and inflammation, is mediated by two receptor families: nicotinic (nAChRs) and muscarinic (mAChRs) acetylcholine receptors, along with two enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), responsible for acetylcholine breakdown. Conventional drugs targeting these components frequently cause off-target effects due to their broad action profiles.
The review article discusses two classes of compounds—photocleavable ligands, which irreversibly release active molecules upon light exposure, and photoswitchable ligands— which can reversibly switch between active and inactive states with light of specific wavelengths. Compared to the conventional targeting methods, the photoactive compounds can offer unprecedented spatial and temporal control over drug action, opening new possibilities in treating diseases like Alzheimer’s, schizophrenia, and inflammatory disorders. The review also catalogs over 40 such compounds, including ligands that selectively modulate α7 nAChRs, M1/M2 mAChRs, and both AChE and BuChE.
The authors suggest that photopharmacology holds potential to support the development of more targeted therapeutic strategies by enabling spatial and temporal control over drug activity, contributing to studying and potentially managing neurodegenerative and inflammatory conditions. This approach may help reduce systemic side effects and improve treatment specificity, transforming the treatment of various disorders through precise and effective therapies. Cholinergic photopharmacology holds promise for innovative precision medicine, particularly in neurodegenerative diseases through light-regulated, noninvasive, and potentially reversible control of neuronal circuits with exceptional accuracy.
Reference article:
“Light‐Activated Pharmacological Tools for Exploring the Cholinergic System”. Alessio Colleoni, Giulia Galli, Clelia Dallanoce, Marco De Amici, Pau Gorostiza, Carlo Matera. Medicinal Research Reviews, 2025; 1–24. https://doi.org/10.1002/med.22108
