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Current Topics in Peptide & Protein Research   Volumes    Volume 17 
Neuronal enhancement substances and trace amine-associated receptor modulators in the therapy of neurodegenerative diseases and brain aging
L. Denes, F. Erdo
Pages: 37 - 44
Number of pages: 8
Current Topics in Peptide & Protein Research
Volume 17 

Copyright © 2016 Research Trends. All rights reserved

Biogenic amines are endogenous molecules that play regulatory roles as neurotransmitters in the brain at nanomolar concentrations. Classical monoamines such as dopamine, norepinephrine, serotonin, and histamine, are formed by decarboxylation of amino acids. Biogenic amines are widely present in the central nervous system and are essential to normal neurophysiological and behavioral function. Trace amines (TAs) are structurally related to classical monoamines, but they exert their effects at extremely small concentrations. Trace amine-associated receptor 1 (TAAR1), discovered at the turn of the 21st century, is an evolutionarily conserved G protein-coupled receptor that is responsive to TAs and structurally related amphetamines. Beta-phenylethylamine (PEA) and tryptamine are endogenous ligands of TAAR1, and regulate neuronal cell function. Synthetic derivatives of PEA and tryptamine act as neuroenhancement substances and offer novel therapeutic avenues in neuropharmacology. Such molecules cross the blood-brain barrier (BBB) without restriction, and affect neuronal cells both directly and indirectly. (-)-Deprenyl is a derivative of PEA and enhances the activity of catecholaminergic neurons. (-)-1-(Benzofuran-2-yl)-2-propylaminopentane or (-)-BPAP enhances the activity of both catecholaminergic and serotonergic neurons at very low doses. In this review we summarize recent developments in the study of neuromodulators, as well as the relevance and applications of TAAR1-targeted drugs in the clinical management of neurodegenerative diseases, neuropsychiatric disorders, and age-related cognitive decline. The mechanism of action of these drugs is thought to involve, among others, restoration of BBB function that is compromised in neurodegenerative and ischemic disorders such as stroke, Alzheimer’s disease and Parkinson’s disease, and also deteriorates with age.
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