A convergence of preclinical pharmacology, and human autopsy and genetic data support the existence of reduced expression and function of the alpha7 nicotinic receptor in patients with schizophrenia. The alpha7 nicotinic receptor is a member of a family of ligand-gated ion channels. The alpha7 nicotinic receptor may play an essential role in auditory sensory gating and voluntary smooth pursuit eye movements, two psychophysiological functions that are abnormal in patients with schizophrenia and closely related unaffected biological relatives. Diminished expression or function of the alpha7 nicotinic receptor in schizophrenia has stimulated consideration of selective full or partial alpha7 nicotinic receptor agonists as possible therapeutic interventions for this disorder. Further, the availability of positive allosteric modulators of nicotinic receptors that can improve the efficiency of transduction of the acetylcholine signal and prevent the rapid desensitization of the receptor should encourage these novel treatment approaches (e.g., galantamine).
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Mol Biol Rep
January 2025
Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
Background: Exposure to ionizing radiation is inevitable due to its extensive use in industrial and medical applications. The search for effective and safe natural therapeutic agents as alternatives to chemical drugs is crucial to mitigate their side effects. This study aimed to evaluate the effects of citicoline as a standalone treatment or in combination with the anti-hepatotoxic drug silymarin in protecting against liver injury caused by γ-radiation in rats.
View Article and Find Full Text PDFBiochem Pharmacol
January 2025
The Marine Science Institute, University of the Philippines Diliman, Quezon City 1101, Philippines. Electronic address:
Conusvenoms are composed of peptides that are commonly post-translationally modified, increasing their chemical diversity beyond what is encoded in the genome and enhancing their potency and selectivity. This study describes how PTMs alter an α-conotoxin's selectivity for specific nAChR subtypes. Venom from the cone snailConus(Asprella)neocostatuswas fractionated using high-performance liquid chromatography and tested using a behavioral intracranial mouse bioassay and a cholinergic calcium imaging assay using SH-SY5Y neuroblastoma cells.
View Article and Find Full Text PDFActa Naturae
January 2024
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997 Russian Federation.
The secreted human protein SLURP-2 is a regulator of epithelial homeostasis, which enhances the viability and migration of keratinocytes. The targets of SLURP-2 in keratinocytes are nicotinic and muscarinic acetylcholine receptors. This work is devoted to the search for the SLURP-2 functional regions responsible for enhancing keratinocyte viability and migration.
View Article and Find Full Text PDFBio Protoc
January 2025
School of Systems Biology, George Mason University, Fairfax, VA, USA.
Nicotinic acetylcholine receptors (nAChRs) are a family of ligand-gated ion channels expressed in nervous and non-nervous system tissue important for memory, movement, and sensory processes. The pharmacological targeting of nAChRs, using small molecules or peptides, is a promising approach for the development of compounds for the treatment of various human diseases including inflammatory and neurogenerative disorders such as Alzheimer's disease. Using the acetylcholine binding protein (Ac-AChBP) as an established structural surrogate for human homopentameric α7 nAChRs, we describe an innovative protein painting mass spectrometry (MS) method that can be used to identify interaction sites for various ligands at the extracellular nAChR site.
View Article and Find Full Text PDFOncogene
January 2025
Department of Pathology, University of California, San Diego, La Jolla, USA.
Smoking plays an underappreciated role in breast cancer progression, increasing recurrence and mortality in patients. Here, we show that S100A8/A9 innate immune signaling is a molecular mechanism that identifies smoking-related breast cancers and underlies their enhanced malignancy. In contrast to acute exposure, chronic nicotine increased tumorigenicity and reprogrammed breast cancer cells to express innate immune response genes.
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