Treating Cocaine Addiction, Obesity, and Emotional Disorders by Viral Gene Transfer of Butyrylcholinesterase

Abstract

Butyrylcholinesterase (BChE), a plasma enzyme that hydrolyses the neurotransmitter, acetylcholine relatively well, with far lower efficiency than acetylcholinesterase (AChE) but with the capability to degrade a broad range of bioactive esters. AChE is universally understood as essential to cholinergic neurotransmission, voluntary muscle performance, and cognition, among other roles, and its catalytic impact is essential for life. A total absence of BChE activity, whether by enzyme inhibition or simple lack of enzyme protein is not only compatible with life, but does not lead to obvious physiologic disturbance. However, very recent studies at Mayo Clinic have amassed support for the concept that BChE does have a true physiological role as a “ghrelin hydrolase” and, pharmacologically, as a cocaine hydrolase. Human subjects and animal mutations that lack functional BChE show higher than normal levels of ghrelin, an acylated peptide that drives hunger and feeding, along with certain emotional behaviors. Mice treated by viral gene transfer of BChE show higher plasma levels of enzyme and lower levels of ghrelin. Ghrelin is acknowledged as a driver of food-seeking and stress. This brief review examines some key phenomena and considers means of modulating BChE as treatments for cocaine addiction, anxiety, aggression, and obesity.

Risk assessment of glycoalkaloids in feed and food, in particular in potatoes and potato‐derived products

“…Recently, it was discovered that BuChE acts also as an esterase of ghrelin (Brimijoin et al, 2016(Brimijoin et al, , 2018. Ghrelin is an orexigenic hormone, produced by the pancreas and mucosa of the stomach and stimulating the appetite via inducing the secretion of neuropeptide Y in the hypothalamus.…”

Biphasic Alteration of Butyrylcholinesterase (BChE) During Prostate Cancer Development

“…BChE has been and remains a very appealing biomarker in cancer diagnosis owing to the common reduction of plasma BChE in multiple cancer types and the general association of the decrease with poor prognosis [19] . This concept is becoming even more attractive by the recent demonstration that BChE hydrolyzes ghrelin [15] , [17] , thus regulating metabolism. Alteration of metabolism is a major contributor of tumorigenesis and cancer progression [45] .…”

“…AChE hydrolyzes acetylcholine rapidly [9] , which is consistent with its classic role in hydrolyzing acetylcholine in cholinergic synapses of the brain and autonomic nervous system [11] . Liver-produced BChE is secreted into serum [12] ; the plasma BChE hydrolyzes butyrylcholine [12] , succinylcholine [13] , and ghrelin (the hunger hormone) [14] , [15] , [16] , [17] . The serum level of BChE is changed in numerous clinical conditions.…”

Acetylcholinesterase: The “Hub” for Neurodegenerative Diseases and Chemical Weapons Convention

“…BChE is found in plasma, being responsible for hydrolysis of different esters, property that has been studied to understand a series of metabolic events or for treatment of cocaine addiction, for example. Furthermore, it has been extensively studied due to its stoichiometric reaction with organophosphorus compounds, which indicates that it is not only a biomarker of exposure to these toxic chemicals but also a potential treatment for intoxication, acting as bioscavenger of nerve agents [61][62][63][64][65][66][67][74][75][76][77][78][79][80][81][82][83].…”

“…Finally, the acyl pocket site (APS) is the point where the difference between AChE and BChE may be assessed, with AChE having a smaller APS than BChE, determining the size of the substrate to be hydrolyzed [61][62][63][64][65][66][67][85][86][87][88][89][90][91][92][93]. Biomolecules 2020, 10, x 6 of 21 these toxic chemicals but also a potential treatment for intoxication, acting as bioscavenger of nerve agents [61][62][63][64][65][66][67][74][75][76][77][78][79][80][81][82][83].…”