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Table 1 Comparison between ALDH1A1 and ALDH2, in terms of expression, biochemistry and PD-related aspects

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

Cytosol [40, 105, 106]

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]

4-HNE and MDA [122,123,124]

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:

- 4-HNE and MDA [135, 136]

- DOPAL (> 5 μM) [121, 136]

- 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]

  1. *The “Enzyme Inhibition” and “In vivo models” sections refer to both ALDH1A1 and ALDH2