Confirmation of a dopamine metabolite in parkinsonian brain tissue by gas chromatography—mass spectrometry

Mattammal, Michael B.; Chung, Hyung D.; Strong, Randy; Hsu, Fong‐Fu

doi:10.1016/0378-4347(93)80310-z

Cited by 38 publications

(37 citation statements)

References 16 publications

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“…However, we did not detect tyrosinase protein in the A9 nigral DA neurons in the human brain by using antibodies against human tyrosinase (Ikemoto et al, 1998). DOPAL was identified in the PD brain, but not in the normal brain, by gas chromatography-mass spectrometry (Mattammal et al, 1993), and was suggested to be toxic for DA neurons in vitro (Mattammal et al, 1995). However, DA depletion in DA-deficient mice did not protect against acute MPTP toxicity in vivo, suggesting that DA does not contribute to this toxicity in vivo (Hasbani et al, 2005).…”

Section: Neurotoxic Substances Producing Pd In Humans and Animalsmentioning

confidence: 64%

Cellular and Molecular Mechanisms of Parkinson’s Disease: Neurotoxins, Causative Genes, and Inflammatory Cytokines

2006

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1. Parkinson's disease (PD) is considered to be an aging-related neurodegeneration of catecholamine (CA) systems [typically A9 dopamine (DA) neurons in the substantia nigra and A6 noradrenaline (NA) neurons in the locus coeruleus]. The main symptom is movement disorder caused by a DA deficiency at the nerve terminals of fibers that project from the substantia nigra to the striatum. Most PD is sporadic (sPD) without any hereditary history. sPD is speculated to be caused by some exogenous or endogenous substances that are neurotoxic toward CA neurons, which toxicity leads to mitochondrial dysfunction and subsequent oxidative stress resulting in the programmed cell death (apoptosis or autophagy) of DA neurons. 2. Recent studies on the causative genes of rare familial PD (fPD) cases, such as alpha-synuclein and parkin, suggest that dysfunction of the ubiquitin-proteasome system (UPS) and the resultant accumulation of misfolded proteins and endoplasmic reticulum stress may cause the death of DA neurons. 3. Activated microglia, which accompany an inflammatory process, are present in the nigro-striatum of the PD brain; and they produce protective or toxic substances, such as cytokines, neurotrophins, and reactive oxygen or nitrogen species. These activated microglia may be neuroprotective at first in the initial stage, and later may become neurotoxic owing to toxic change to promote the progression toward the death of CA neurons.4. All of these accumulating evidences on sPD and fPD points to a hypothesis that multiple primary causes of PD may be ultimately linked to a final common signal-transduction pathway leading to programmed cell death, i.e., apoptosis or autophagy, of the CA neurons.

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Section: Neurotoxic Substances Producing Pd In Humans and Animalsmentioning

confidence: 64%

Cellular and Molecular Mechanisms of Parkinson’s Disease: Neurotoxins, Causative Genes, and Inflammatory Cytokines

2006

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“…Although as early as 1952 it had been suggested that products of the enzymatic oxidation of catecholamines, catecholaldehydes, are potentially toxic (Blaschko, 1952), the first report about measurement of DOPAL in human brain was published in 1993 (Mattammal et al, 1993). …”

Section: The Catecholaldehyde Hypothesismentioning

confidence: 99%

Catecholamine autotoxicity. Implications for pharmacology and therapeutics of Parkinson disease and related disorders

Goldstein

Kopin

Sharabi

2014

Pharmacology & Therapeutics

138

121

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Several neurodegenerative diseases involve loss of catecholamine neurons—Parkinson disease is a prototypical example. Catecholamine neurons are rare in the nervous system, and why they are vulnerable in PD and related disorders has been mysterious. Accumulating evidence supports the concept of “autotoxicity”—inherent cytotoxicity of catecholamines and their metabolites in the cells in which they are produced. According to the “catecholaldehyde hypothesis” for the pathogenesis of Parkinson disease, long-term increased build-up of 3,4-dihydroxyphenylacetaldehyde (DOPAL), the catecholaldehyde metabolite of dopamine, causes or contributes to the eventual death of dopaminergic neurons. Lewy bodies, a neuropathologic hallmark of PD, contain precipitated alpha-synuclein. Bases for the tendency of alpha-synuclein to precipitate in the cytoplasm of catecholaminergic neurons have also been mysterious. Since DOPAL potently oligomerizes and aggregates alpha-synuclein, the catecholaldehyde hypothesis provides a link between alpha-synucleinopathy and catecholamine neuron loss in Lewy body diseases. The concept developed here is that DOPAL and alpha-synuclein are nodes in a complex nexus of interacting homeostatic systems. Dysfunctions of several processes, including decreased vesicular sequestration of cytoplasmic catecholamines, decreased aldehyde dehydrogenase activity, and oligomerization of alpha-synuclein, lead to conversion from the stability afforded by negative feedback regulation to the instability, degeneration, and system failure caused by induction of positive feedback loops. These dysfunctions result from diverse combinations of genetic predispositions, environmental exposures, stress, and time. The notion of catecholamine autotoxicity has several implications for treatment, disease modification, and prevention. Conversely, disease modification clinical trials would provide key tests of the catecholaldehyde hypothesis.

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“…Attempts have been made to synthesize pure DOPAL (22)(23)(24)(25). However, none of the methods provide detailed procedures and physical or chemical characterization of DOPAL other than its molecular weight by GC-MS.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of a Biochemically Important Aldehyde, 3,4-Dihydroxyphenylacetaldehyde

Spaziano

Burke

1998

Bioorganic Chemistry

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3,4-Dihydroxyphenylacetaldehyde (DOPAL) is an important precursor of the major brain metabolites of dopamine, 3,4-dihydroxyphenylacetic acid and 4-hydroxy-3-methoxyphenylacetic acid. A new method for the synthesis of DOPAL from piperonal is described. We report for the first time the physical and chemical characteristics of DOPAL. Its importance for research in Parkinson's disease and Alzheimer's disease is discussed.

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Confirmation of a dopamine metabolite in parkinsonian brain tissue by gas chromatography—mass spectrometry

Cited by 38 publications

References 16 publications

Cellular and Molecular Mechanisms of Parkinson’s Disease: Neurotoxins, Causative Genes, and Inflammatory Cytokines

Cellular and Molecular Mechanisms of Parkinson’s Disease: Neurotoxins, Causative Genes, and Inflammatory Cytokines

Catecholamine autotoxicity. Implications for pharmacology and therapeutics of Parkinson disease and related disorders

Synthesis of a Biochemically Important Aldehyde, 3,4-Dihydroxyphenylacetaldehyde

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