From: Impaired dopamine metabolism in Parkinson’s disease pathogenesis
ALDH1A1 | ALDH2 | |
Tissue expression | Brain, eye lens, retina, lung, liver, kidney, testis [104] | Liver, kidney, heart, lung, brain [104] |
Subcellular localization | Mitochondrial matrix [104] | |
Substrates | Retinaldehyde (km < 0.1 μM) [116] DOPAL (km 0.4 μM) [24, 113, 114] 4-HNE (km 4.8 μM [117]; 17.9 μM [118]) MDA (km 3.5 μM [117]; 114.4 μM [119]) Ƴ-aminobutyraldehyde (800 μM) [112] | Acetaldehyde (km < 1 μM) [120] DOPAL (km 1 μM) [121] Ƴ-aminobutyraldehyde (500 μM) [112] |
PD-related | ||
Genetic variants | N.A | - Haplotype: rs737280; rs968529; rs16941667; rs16941669; rs9971942 (California) [125] - Haplotype: rs4767944; rs441; rs671 (China) [126] - rs671 SNP (China) [127] |
Expression levels | Reduced mRNA levels: - TH-positive neurons in PD patients’ brain [128] - transgenic A53T mouse striatum [129] | N.A. |
Decreased protein levels: - PD patients’ brain [130, 131] -LRRK2-G2019S knock-in mouse DA neurons [132] | ||
Enzyme inhibition * | Epidemiological studies: - traces of Dieldrin in tissues of exposed PD patients [133] - Benomyl exposure correlates with PD risk [134] | |
In vitro: - Benomyl [134] | ||
Cellular models of ALDH inhibition: - rat purified synaptosomes treated with 4-HNE and MDA [34] - SH-SY5Y cells treated with Disulfiram [137] - Neurons from Daidzin administered hamster [138] - PC6–3 cells treated with Dieldrin [139] - primary neurons and SK-N-MC cells treated with Benomyl [134] | ||
In vivo models * | Genetic models: - A53T/Aldh1a1−/−mouse [40] - Aldh1a1−/−/Aldh2−/− mouse [28] - Aldh1a1−/−/Gpx−/− mouse [140] | |
Toxin-based models: - Benomyl intraperitoneally administered mouse [141] - Benomyl exposed zebrafish embryos [134] - Ziram exposed zebrafish embryos [142] |