Abstract
Aromatic L-amino acid decarboxylase (AAAD) is the second enzyme in the sequence leading to the synthesis of the catecholamines and serotonin, and it is the rate-limiting enzyme for the synthesis of the trace amines. In the striatum AAAD activity is increased by neuronal firing and diminished or enhanced by activation or blocking dopamine (DA) D1 or D2 receptors, respectively. At least two biochemical mechanisms appear responsible for modulation, short-term involving second messengers and possible phosphorylation, and long-term involving protein synthesis. In Parkinson's disease AAAD is the rate-controlling enzyme for the synthesis of DA when L-DOPA is administered and any change of AAAD activity could have clinical consequences. Indeed, the "on-off phenomenon" where there are fluctuations between off-periods of marked akinesia over several hours with on-periods of improved motility may be related to oscillating or poorly modulated AAAD activity and conversion of L-DOPA to DA. Studies are presented demonstrating how AAAD activity can be enhanced in an animal model of Parkinson's disease and how rapid fluctuations of AAAD can be provoked via second messenger system activation.
Citations
Dec 12, 2001·Endocrine Reviews·N Ben-Jonathan, R Hnasko
Aug 14, 2013·PloS One·De-Fen ShihShyh-Jye Lee
Sep 24, 2005·Neurochemical Research·Alice-Georgia VassiliouEmmanuel G Fragoulis
Aug 3, 2004·Acta Neurologica Scandinavica·Y KumakuraP Cumming
Apr 24, 2003·Synapse·Raúl De La Fuente-FernándezA Jon Stoessl
Nov 15, 2011·Brain : a Journal of Neurology·Ramachandiran NandhagopalA Jon Stoessl
Jun 16, 2001·Synapse·E H DanielsenP Cumming
Jul 7, 1999·Neuroscience·S E LeffR J Mandel
Jun 16, 2000·Brain Research·A Fisher, M S Starr
Jun 15, 1999·Brain Research·S ChoM Hadjiconstantinou
Jun 1, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Andreas HahnRupert Lanzenberger
Dec 13, 2006·Brain Research·Francesco FornaiAntonio Paparelli
Feb 13, 2003·Neurology·J Eric Ahlskog
Feb 24, 2009·Molecular Genetics and Metabolism·George F G AllenSimon J R Heales