David S Goldstein1, Patricia Sullivan2, Courtney Holmes2, Irwin J Kopin2, Yehonatan Sharabi3, Deborah C Mash4. 1. Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA. Electronic address: goldsteind@ninds.nih.gov. 2. Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA. 3. Department of Internal Medicine, Chaim Sheba Medical Center, Tel-HaShomer, and Sackler Faculty of Medicine, Tel-Aviv University, Israel. 4. Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA.
Abstract
BACKGROUND: Parkinson disease (PD) and multiple system atrophy (MSA) share some neuropathologic features (nigrostriatal dopaminergic lesion, alpha-synuclein deposition) but not others (Lewy bodies in PD, glial cytoplasmic inclusions in MSA). In PD evidence has accrued for a vesicular storage defect and decreased aldehyde dehydrogenase (ALDH) activity in residual dopaminergic terminals, resulting in accumulation of the toxic dopamine (DA) metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL). In this study we asked whether MSA entails a similar abnormal neurochemical pattern. METHODS: DA and its main neuronal metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), norepinephrine (NE) and its main neuronal metabolite 3,4-dihydroxyphenylglycol (DHPG), the catecholamine precursor DOPA, and DOPAL were measured in striatal and frontal cortical tissue from patients with pathologically proven end-stage MSA (N = 15), sporadic PD (N = 17), and control subjects (N = 18). RESULTS: Compared to the control group, the MSA and PD groups had similarly decreased putamen DA (by 96% and 93%, p < 0.0001), DOPAC (97% and 95%, p < 0.0001), NE (91% and 74%, p < 0.0001), and DHPG (81% and 74%, p < 0.0001). In the MSA and PD groups, ratios of DOPAL:DA were 2.3 and 3.5 times control and DHPG:NE 3.1 and 2.6 times control, while DOPAC:DOPAL ratios were decreased by 61% and 74%. In both diseases cortical NE and DHPG were decreased, while DA and DOPAC were not. CONCLUSIONS: MSA and PD entail a catecholamine metabolic profile indicating impaired vesicular storage, decreased ALDH activity, and DOPAL buildup, which might be part of a common pathway in catecholamine neuronal death. Targeting this pathway by interfering with catecholaldehyde production or effects constitutes a novel treatment approach. Published by Elsevier Ltd.
BACKGROUND:Parkinson disease (PD) and multiple system atrophy (MSA) share some neuropathologic features (nigrostriatal dopaminergic lesion, alpha-synuclein deposition) but not others (Lewy bodies in PD, glial cytoplasmic inclusions in MSA). In PD evidence has accrued for a vesicular storage defect and decreased aldehyde dehydrogenase (ALDH) activity in residual dopaminergic terminals, resulting in accumulation of the toxic dopamine (DA) metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL). In this study we asked whether MSA entails a similar abnormal neurochemical pattern. METHODS:DA and its main neuronal metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), norepinephrine (NE) and its main neuronal metabolite 3,4-dihydroxyphenylglycol (DHPG), the catecholamine precursor DOPA, and DOPAL were measured in striatal and frontal cortical tissue from patients with pathologically proven end-stage MSA (N = 15), sporadic PD (N = 17), and control subjects (N = 18). RESULTS: Compared to the control group, the MSA and PD groups had similarly decreased putamen DA (by 96% and 93%, p < 0.0001), DOPAC (97% and 95%, p < 0.0001), NE (91% and 74%, p < 0.0001), and DHPG (81% and 74%, p < 0.0001). In the MSA and PD groups, ratios of DOPAL:DA were 2.3 and 3.5 times control and DHPG:NE 3.1 and 2.6 times control, while DOPAC:DOPAL ratios were decreased by 61% and 74%. In both diseases cortical NE and DHPG were decreased, while DA and DOPAC were not. CONCLUSIONS: MSA and PD entail a catecholamine metabolic profile indicating impaired vesicular storage, decreased ALDH activity, and DOPAL buildup, which might be part of a common pathway in catecholamineneuronal death. Targeting this pathway by interfering with catecholaldehyde production or effects constitutes a novel treatment approach. Published by Elsevier Ltd.
Entities:
Keywords:
DOPAL; Dopamine; Multiple system atrophy; Norepinephrine; Parkinson disease; Putamen
Authors: David S Goldstein; Patricia Sullivan; Courtney Holmes; Gary W Miller; Yehonatan Sharabi; Irwin J Kopin Journal: J Neurochem Date: 2014-06-13 Impact factor: 5.372
Authors: I Litvan; C G Goetz; J Jankovic; G K Wenning; V Booth; J J Bartko; A McKee; K Jellinger; E C Lai; J P Brandel; M Verny; K R Chaudhuri; R K Pearce; Y Agid Journal: Arch Neurol Date: 1997-08