Biogenic Aldehyde-Mediated Mechanisms of Toxicity in Neurodegenerative Disease

Overview

Journal Curr Opin Toxicol

Date 2019 Jul 16

PMID 31304429

Citations 18

Authors

Brianna S Cagle

Rachel A Crawford

Jonathan A Doorn

Affiliations

Soon will be listed here.

Abstract

Oxidative decomposition of several biomolecules produces reactive aldehydes. Monoamine neurotransmitters are enzymatically converted to aldehydes via monoamine oxidase followed by further metabolism such as carbonyl oxidation/reduction. Elevated levels of aldehyde intermediates are implicated as factors in several pathological conditions, including Parkinson's disease. The biogenic aldehydes produced from dopamine, norepinephrine and serotonin are known to be toxic, generate reactive oxygen species and/or cause aggregation of proteins such as α-synuclein. Polyunsaturated lipids undergo oxidative decomposition to produce biogenic aldehydes, including 4-hydroxy-2-nonenal and malondialdehyde. These lipid aldehydes, some including an α,β-unsaturated carbonyl, target important proteins such as α-synuclein, proteasome degradation and G-protein-coupled signaling. Overproduction of biogenic aldehydes is a hypothesized factor in neurodegeneration; preventing their formation or scavenging may provide means for neuroprotection.

Citing Articles

Selective dopaminergic neurotoxicity modulated by inherent cell-type specific neurobiology.

Currim F, Tanwar R, Brown-Leung J, Paranjape N, Liu J, Sanders L Neurotoxicology. 2024; 103:266-287.

PMID: 38964509 PMC: 11288778. DOI: 10.1016/j.neuro.2024.06.016.

Neuroprotective Effects of Aldehyde-Reducing Composition in an LPS-Induced Neuroinflammation Model of Parkinson's Disease.

Kang S, Noh Y, Oh S, Yoon H, Im S, Kwon H Molecules. 2023; 28(24).

PMID: 38138478 PMC: 10745824. DOI: 10.3390/molecules28247988.

Aldehyde-Associated Mutagenesis─Current State of Knowledge.

Vijayraghavan S, Saini N Chem Res Toxicol. 2023; 36(7):983-1001.

PMID: 37363863 PMC: 10354807. DOI: 10.1021/acs.chemrestox.3c00045.

Scavenging neurotoxic aldehydes using lysine carbon dots.

Bloch D, Sandre M, Ben Zichri S, Masato A, Kolusheva S, Bubacco L Nanoscale Adv. 2023; 5(5):1356-1367.

PMID: 36866263 PMC: 9972859. DOI: 10.1039/d2na00804a.

Harnessing the Therapeutic Potential of the Nrf2/Bach1 Signaling Pathway in Parkinson's Disease.

Ahuja M, Kaidery N, Dutta D, Attucks O, Kazakov E, Gazaryan I Antioxidants (Basel). 2022; 11(9).

PMID: 36139853 PMC: 9495572. DOI: 10.3390/antiox11091780.

References

Wallace D . Mitochondrial diseases in man and mouse. Science. 1999; 283(5407):1482-8. DOI: 10.1126/science.283.5407.1482. View

BURKE W, Chung H, Li S . Quantitation of 3,4-dihydroxyphenylacetaldehyde and 3, 4-dihydroxyphenylglycolaldehyde, the monoamine oxidase metabolites of dopamine and noradrenaline, in human tissues by microcolumn high-performance liquid chromatography. Anal Biochem. 1999; 273(1):111-6. DOI: 10.1006/abio.1999.4196. View

Linert W, Jameson G . Redox reactions of neurotransmitters possibly involved in the progression of Parkinson's Disease. J Inorg Biochem. 2000; 79(1-4):319-26. DOI: 10.1016/s0162-0134(99)00238-x. View

BURKE W, Li S, Zahm D, Macarthur H, Kolo L, Westfall T . Catecholamine monoamine oxidase a metabolite in adrenergic neurons is cytotoxic in vivo. Brain Res. 2001; 891(1-2):218-27. DOI: 10.1016/s0006-8993(00)03199-1. View

Kristal B, Conway A, Brown A, Jain J, Ulluci P, Li S . Selective dopaminergic vulnerability: 3,4-dihydroxyphenylacetaldehyde targets mitochondria. Free Radic Biol Med. 2001; 30(8):924-31. DOI: 10.1016/s0891-5849(01)00484-1. View

Li S, Lin T, Minteer S, BURKE W . 3,4-Dihydroxyphenylacetaldehyde and hydrogen peroxide generate a hydroxyl radical: possible role in Parkinson's disease pathogenesis. Brain Res Mol Brain Res. 2001; 93(1):1-7. DOI: 10.1016/s0169-328x(01)00120-6. View

Doorn J, Petersen D . Covalent modification of amino acid nucleophiles by the lipid peroxidation products 4-hydroxy-2-nonenal and 4-oxo-2-nonenal. Chem Res Toxicol. 2002; 15(11):1445-50. DOI: 10.1021/tx025590o. View

BLASCHKO H . Amine oxidase and amine metabolism. Pharmacol Rev. 1952; 4(4):415-58. View

Burke W, Li S, Chung H, Ruggiero D, Kristal B, Johnson E . Neurotoxicity of MAO metabolites of catecholamine neurotransmitters: role in neurodegenerative diseases. Neurotoxicology. 2003; 25(1-2):101-15. DOI: 10.1016/S0161-813X(03)00090-1. View

10.

Eisenhofer G, Kopin I, Goldstein D . Catecholamine metabolism: a contemporary view with implications for physiology and medicine. Pharmacol Rev. 2004; 56(3):331-49. DOI: 10.1124/pr.56.3.1. View

11.

Zecca L, Youdim M, Riederer P, Connor J, Crichton R . Iron, brain ageing and neurodegenerative disorders. Nat Rev Neurosci. 2004; 5(11):863-73. DOI: 10.1038/nrn1537. View

12.

Adinoff B . Neurobiologic processes in drug reward and addiction. Harv Rev Psychiatry. 2005; 12(6):305-20. PMC: 1920543. DOI: 10.1080/10673220490910844. View

13.

Miyamoto S, Howes A, Adams J, Dorn 2nd G, Brown J . Ca2+ dysregulation induces mitochondrial depolarization and apoptosis: role of Na+/Ca2+ exchanger and AKT. J Biol Chem. 2005; 280(46):38505-12. DOI: 10.1074/jbc.M505223200. View

14.

Squires L, Jakubowski J, Stuart J, Rubakhin S, Hatcher N, Kim W . Serotonin catabolism and the formation and fate of 5-hydroxyindole thiazolidine carboxylic acid. J Biol Chem. 2006; 281(19):13463-13470. DOI: 10.1074/jbc.M602210200. View

15.

Florang V, Rees J, Brogden N, Anderson D, Hurley T, Doorn J . Inhibition of the oxidative metabolism of 3,4-dihydroxyphenylacetaldehyde, a reactive intermediate of dopamine metabolism, by 4-hydroxy-2-nonenal. Neurotoxicology. 2006; 28(1):76-82. DOI: 10.1016/j.neuro.2006.07.018. View

16.

Marchitti S, Deitrich R, Vasiliou V . Neurotoxicity and metabolism of the catecholamine-derived 3,4-dihydroxyphenylacetaldehyde and 3,4-dihydroxyphenylglycolaldehyde: the role of aldehyde dehydrogenase. Pharmacol Rev. 2007; 59(2):125-50. DOI: 10.1124/pr.59.2.1. View

17.

Rees J, Florang V, Anderson D, Doorn J . Lipid peroxidation products inhibit dopamine catabolism yielding aberrant levels of a reactive intermediate. Chem Res Toxicol. 2007; 20(10):1536-42. DOI: 10.1021/tx700248y. View

18.

Esterbauer H, Schaur R, Zollner H . Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med. 1991; 11(1):81-128. DOI: 10.1016/0891-5849(91)90192-6. View

19.

Jinsmaa Y, Florang V, Rees J, Anderson D, Strack S, Doorn J . Products of oxidative stress inhibit aldehyde oxidation and reduction pathways in dopamine catabolism yielding elevated levels of a reactive intermediate. Chem Res Toxicol. 2009; 22(5):835-41. PMC: 2696154. DOI: 10.1021/tx800405v. View

20.

Rees J, Florang V, Eckert L, Doorn J . Protein reactivity of 3,4-dihydroxyphenylacetaldehyde, a toxic dopamine metabolite, is dependent on both the aldehyde and the catechol. Chem Res Toxicol. 2009; 22(7):1256-63. PMC: 2717024. DOI: 10.1021/tx9000557. View