Brain choline esterase

Autopsy studies on Alzheimer-afflicted brains some 40 years later showed a similar huge drop in neurotransmitter levels, but this time it was acetylcholine (ACh) in the hippocampus —which is associated with memory. Choline-esterase inhibitors, which stop the breakdown of ACh, were introduced and are presently the only symptom treatment available (Aricept, Excelon, Reminyl, Cognex). Recently, in 2004, memantine was approved as the first treatment to slow progression of Alzheimer s in mild to moderate cases. Work is ongoing to define acetylcholine-like muscarinic M-1 agonists and M-2 agonists that act on acetylcholine receptors directly. 

Two related enzymes have the ability to hydrolyze acetylcholine. One is acetylcholinesterase (EC 3.1.1.7, acetylcholine acetyUiydrolase), which is called true cholinesterase or choline esterase I. True cholinesterase is found in erythrocytes, the lungs and spleen, nerve endings, and the gray matter of the brain. It is responsible for the prompt hydrolysis of acetylcholine released at the nerve endings to mediate transmission of the neural impulse across the synapse. The degradation of acetylcholine is required for the depolarization of the nerve so that it is repolarized in the next conduction event. 

The other cholinesterase is acylcholine acylhydrolase (EC 3.1.1.8, acylcholine acylhydrolase, CHE) it is also called pseudocholinesterase, serum cholinesterase, butyryl-choHnesterase, or choline esterase II. Although it is found in the liver, pancreas, heart, white matter of the brain, and serum, its biological role is unknown. The assay of this enzyme is clinically useful. 

B Oxidative bioactivation of losartan C Methyienedioxy derivatives as bioprecursors of catechols D Site-specific delivery of the acetyl-choline-esterase reactivator 2-PAM to the brain... 

Choline acetylase may also be extracted from powder of acetone-dried brain. In these preparations choline esterase is destroyed to a large extent. Sometimes the destruction of choline esterase is neatly complete. In this way the two enzymes may be separated (Nachmansohn and John, 111)... 

The above authors coimmobilized choline oxidase and AChE on a nylon net which was fixed to a hydrogen peroxide probe so that the esterase was adjacent to the solution. The apparent activities were 200-400 mU/cm2 for choline oxidase and 50-100 mU/cm2 for AChE. The sensitivity of the sequence electrode for ACh was about 90% of that for choline, resulting in a detection limit of 1 pmol/l ACh. The response time was 1-2 min. The parameters of this amperometric sensor surpass those of potentiometric enzyme electrodes for ACh (see Section 3.1.25). Application to brain extract analysis has been announced. 

For this purpose we have determined whether an alkaloid can displace a specifically bound ligand from a neuroreceptor, such as ot, 0t2 adrenergic receptors, serotonin receptor [5-HT2], and nicotinic and muscarinic acetyl choline receptors (Table 15) obtained from porcine brains [69-72]. In addition, we have determined whether the same alkaloids inhibit acetylcholine esterase, whether they intercalate DNA, inhibit DNA polymerase I, reverse transcriptase, protein biosynthesis and membrane stability [40, 73]. The results can be summarized as follows ... 

---