Aldehyde dehydrogenase inhibition as a pathogenic mechanism in
Here we propose that benomyl, via its bioactivated thiocarbamate sulfoxide metabolite, inhibits aldehyde dehydrogenase (ALDH), leading to accumulation of the reactive dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), preferential degeneration of dopaminergic neurons, and development of PD.
Benomyl, aldehyde dehydrogenase, DOPAL, and the
Abstract The dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) is detoxified mainly by aldehyde dehydrogenase (ALDH). We find that the fungicide benomyl potently and rapidly inhibits ALDH and builds up DOPAL in vivo in mouse striatum and in vitro in PC12 cells and human cultured fibroblasts and glial cells.
Rotenone decreases intracellular aldehyde dehydrogenase activity
Comparison of rotenone (red, a) with benomyl (blue, b) effects on DOPAL (circles) and 3,4-dihydroxyphenylacetic acid (DOPAC) (squares) levels and DOPAC:DOPAL ratios (c) in test tubes after incubation with aldehyde dehydrogenase (ALDH)2 and NAD +. Benomyl potently inhibited conversion of DOPAL to DOPAC, whereas rotenone exerted only a mild effect.
Aldehyde dehydrogenase inhibition as a pathogenic mechanism
Here we propose that benomyl, via its bioactivated thiocarbamate sulfoxide metabolite, inhibits aldehyde dehydrogenase (ALDH), leading to accumulation of the reactive dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), preferential degeneration of dopaminergic neurons, and development of PD.
Phytoconstituents in the Management of Pesticide Induced
Benomyl, a benzimidazole fungicide is being widely used in India in cultivation of tropical crops. Studies prove the chronic exposure of benomyl leads to aldehyde dehydrogenase inhibition...
- Does fungicide benomyl inhibit aldehyde dehydrogenase?
- The dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) is detoxified mainly by aldehyde dehydrogenase (ALDH). We find that the fungicide benomyl potently and rapidly inhibits ALDH and builds up DOPAL in vivo in mouse striatum and in vitro in PC12 cells and human cultured fibroblasts and glial cells.
- What is dopamine metabolite?
- The toxic dopamine (DA) metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) is formed from mitochondrial monoamine oxidase (MAO) acting on cytoplasmic DA. DOPAL cytotoxicity occurs via oxidative injury and protein cross-linking. DOPAL is detoxified by aldehyde dehydrogenase (ALDH) to form 3,4-dihydroxyphenylacetic acid (DOPAC).
- What is the catecholaldehyde hypothesis for PD?
- Catecholaldehyde hypothesis for PD. The toxic dopamine (DA) metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) is formed from mitochondrial monoamine oxidase (MAO) acting on cytoplasmic DA. DOPAL cytotoxicity occurs via oxidative injury and protein cross-linking.
- How does DOPAL cytotoxicity occur?
- DOPAL cytotoxicity occurs via oxidative injury and protein cross-linking. DOPAL is detoxified by aldehyde dehydrogenase (ALDH) to form 3,4-dihydroxyphenylacetic acid (DOPAC). An alternative metabolite is 3,4-dihydroxyphenylethanol (DOPET). Rapid Report pubs.acs.org/crt
- Does a dopamine metabolite play a pathogenic role in PD?
- Exposure to pesticides that inhibit ALDH may therefore increase PD risk via DOPAL buildup. This study lends support to the “catecholaldehyde hypothesis” that the autotoxic dopamine metabolite DOPAL plays a pathogenic role in PD. P
- Does 1000 nm benomyl affect glia?
- Time-series studies established the rapid action of 1000 nM benomyl in both human fibroblasts and glia (Figure 3B and C). Thus, in the cells as in the mouse striatum, the principal catechols affected were DOPAL and DOPET increasing and DOPAC decreasing, as expected for ALDH inhibition.
