Are metallothionein genes silenced in ALS?

Sporadic amyotrophic lateral sclerosis (SALS) results from the death of motor neurons in the brain and spinal cord. Environmental exposure to heavy metals has been implicated in SALS and impaired detoxification of these metals may cause susceptibility to the disease. The metallothionein (MT) family of proteins are the primary detoxification mechanism for heavy metals and MT-Ia and MT-IIa are the most common human isoforms. Inappropriate methylation at the promoters of these genes could lead to silencing of transcription and reduce the availability of MTs. We therefore measured the level of methylation in the promoters of MT-Ia and MT-IIa in 25 leukocyte and six brain DNA samples from SALS patients and compared these with controls. No promoter methylation was evident in any SALS or control samples. In conclusion, it is unlikely that methylation at these gene promoters is a common cause of SALS.