Table 2.
Environmental and Lifestyle Factors: Relationship to ALS and Mechanisms of OS
| Factor | Strength of the Association |
Mechanisms of Oxidative Stress Toxicity |
|---|---|---|
| Agricultural chemicals |
Uncertain (91–99, 104, 193) | Apoptosis and ROS-induced DNA damage (114) PON1 genotype (263); protein carbonyl production (116) mitochondrial damage (122) |
| Lead, other heavy metals |
Uncertain (92, 94, 104, 127, 128, 130, 353) | ↓ cellular GSH (133); ↓ copper homeostasis (134); combined toxicity with other metals (136, 137) |
| Military service | Uncertain (144–146, 148–151, 153) |
Head trauma and ApoE4 genotype (154) |
| Trauma | Uncertain (101, 154– 164, 169) |
Possibly via free radical production (ROS) (172) |
| Strenuous physical activity |
Uncertain (189) | ↓ GSH and ↑ apoptosis (186); ↑ free radicals (187, 354) |
| Professional football | Suspected (165– 168) |
Physical activity per se may not be the cause (166, 190) |
| Diet (high in fat, glutamate) |
Uncertain (193–195) | ↑OS, inflammation, and NF-κB activation in the cerebral cortex (304, 306) |
| Smoking | Suspected (154, 156, 200–209) | Protein and DNA damage, cell death (213), ↑ heavy metal levels (216) |
| Malnutrition/Cachexia | Clinically observed (301, 303) |
↑ OS (300) |
| Hypoxia | Clinically observed (307) |
ROS production via mitochondrial dysfunction (308); ↑ DNA, lipid, protein oxidation (312, 313) |
| Psychological stress | Clinically observed (315, 316) |
OS and shorten telomere length (317); induction of cytokines, apoptosis, and OS (319) |
ApoE = Apoliprotein E, GSH = glutathione, OS = oxidative stress, PON1 = Paraoxonase 1, ROS = reactive oxygen species.