A safe lithium mimetic for bipolar disorder.

Lithium is the most effective mood stabilizer for the treatment of bipolar disorder, but it is toxic at only twice the therapeutic dosage and has many undesirable side effects. It is likely that a small molecule could be found with lithium-like efficacy but without toxicity through target-based drug discovery; however, therapeutic target of lithium remains equivocal. Inositol monophosphatase is a possible target but no bioavailable inhibitors exist.

Cloning, expression, purification, crystallization and X-ray analysis of inositol monophosphatase from Mus musculus and Homo sapiens.

Inositol monophosphatase (IMPase) catalyses the hydrolysis of inositol monophosphate to inositol and is crucial in the phosphatidylinositol (PI) signalling pathway. Lithium, which is the drug of choice for bipolar disorder, inhibits IMPase at therapeutically relevant plasma concentrations. Both mouse IMPase 1 (MmIMPase 1) and human IMPase 1 (HsIMPase 1) were cloned into pRSET5a, expressed in Escherichia coli, purified and crystallized using the sitting-drop method.

From protein to peptides: a spectrum of non-hydrolytic functions of acetylcholinesterase.

Acetylcholinesterase (AChE), a member of the α/β-hydrolase fold superfamily of proteins, is a serine hydrolase responsible for the hydrolysis of the well studied neurotransmitter acetylcholine (ACh). However, it is becoming clear that AChE has a range of actions other than this 'classical' role. Non-classical AChE functions have been identified in apoptosis, stress-responses, neuritogenesis, and neurodegeneration.

Teaching medical students basic neurotransmitter pharmacology using primary research resources.

Teaching pharmacology to medical students has long been seen as a challenge, and one to which a number of innovative approaches have been taken. In this article, we describe and evaluate the use of primary research articles in teaching second-year medical students both in terms of the information learned and the use of the papers themselves. We designed a seminar where small groups of students worked on different neurotransmitters before contributing information to a plenary session.

Evaluation of a technique to identify acetylcholinesterase C-terminal peptides in human serum samples.

A novel theory for neurodegeneration is that non-cholinergic functions of acetylcholinesterase (AChE) are responsible for the progressive death of global neurons. The C-terminal region of AChE has been shown to be responsible for non-cholinergic actions of AChE by binding to an allosteric site on the alpha 7-nicotinic acetylcholine receptor, thereby causing calcium influx; the resultant signal has trophic effects in immature neurons, but toxic effects in mature neurons. Although there is strong in vitro and in vivo evidence for the involvement of this C-terminal region of AChE in neurodegeneration, a cleaved C-terminal peptide has not yet been identified in human brains.