Together, carrying allele G in the single nucleotide polymorphism (rs2070424 A/G) in SOD1, or allele C in the single nucleotide polymorphism (rs4880 T/C) in SOD2, enhances genetic susceptibility to Parkinson's disease.
In two different transgenic (Tg) mouse models of adult-onset neurodegenerative disease, a human A53T-α-synuclein (hαSyn) model of Parkinson's disease (PD) and a human G93A-superoxide dismutase-1(hSOD1) model of amyotrophic lateral sclerosis (ALS), mortality and survivor morbidity were significantly greater than non-Tg mice and a Tg mouse model of Alzheimer's disease after neonatal traumatic brain injury (TBI).
Rasagiline, a monoamine oxidase B inhibitor with neuroprotective potential in Parkinson's disease, has shown a disease-modifying effect in the SOD1-Gly93Ala low-expressing mouse model of amyotrophic lateral sclerosis, both alone and in combination with riluzole.
In the light of the possibility that different SOD1 entities could be expressed also in other neurodegenerative disorders, as a sort of unifying event with AD and PD, we have investigated amyotrophic lateral sclerosis (ALS) using human neuroblastoma SH-SY5Y cells with mutated SOD1 gene H46R as cellular model.