Biogenic aldehyde-mediated mechanisms of toxicity in neurodegenerative disease

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.