Genetic polymorphisms in amyotrophic lateral sclerosis: Evidence for implication in detoxification pathways of environmental toxicants

Abstract

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease of the central nervous system, characterized by progressive loss of motor neurons, and occurring in both sporadic and familial form. The origin of the disease is unknown, though increasing evidence suggests that the interaction between genetic and environmental factors may increase susceptibility to ALS, including its sporadic form. Although genetic mutations have been correlated to the familial type of ALS, relatively little is known about the sporadic type (sALS). Genetic factors concerning pesticide metabolism and heavy metal detoxification are increasing the susceptibility to sALS. This review focuses on the genes implicated in metabolic detoxification pathways of environmental toxicants and their potential role in ALS susceptibility.

New molecular diagnostic trends and biomarkers for amyotrophic lateral sclerosis

“…There are also variants in genes associated with pesticide metabolism or heavy metal detoxification that may increase the susceptibility of SALS by environmental factors. Such genes include the paraoxonases ( PON1 , PON2 , PON3 ), the metallothioneins, and others (Dardiotis et al., ). Finally, variants in the SP110 gene have been shown to modify the risk of degenerative myelopathy in dogs, which is an analog of ALS in humans (Ivansson et al., ).…”

Genetic Risk Factors for Essential Tremor: A Review

“…The d-aminolevulinic acid dehydratase (ALAD) catalyzes the second step in heme synthesis, leading to the production of cobalamin-monopyrrole-porphobilinogen [ 72 73 ], and the ALAD gene has been shown to influence the toxicokinetics of lead [ 74 ]. ALAD gene has one polymorphism, giving way to two codominant alleles, ALAD-1 and ALAD-2 [ 74 ].…”

“…Pathogenic mutations in Fused in sarcoma/Translated in liposarcoma (FUS/TLS) are causing factors for amyotrophic lateral sclerosis (ALS) (4% of familial cases and <1% of sporadic ALS cases) [ 73 102 ] and frontotemporal lobar degeneration (FTLD) [ 103 ].…”

“…The vitamin D receptor (VDR) gene, encodes the vitamin D receptor, and it seems that genetic variability of VDR may also affect lead toxicity [73]. On the other hand, the heme oxygenase (HMOX) enzyme is also involved in heme catabolism.…”

Modulation of dopamine metabolizing enzymes and antioxidant status by Capsicum annuum Lin in rotenone-intoxicated rat brain

“…Susceptibility of dopaminergic cells to oxidative damage is further advanced by defective iron homeostasis. Iron related genes may either cause or predispose such cells to damage, possibly due to the contribution of iron to the synthesis of tyrosine hydroxylase [44,45]. Also, there is some evidence that there is an increase in iron load in the SN of Parkinson’s disease (PD) patients as compared to controls [44].…”