Amyotrophic lateral sclerosis (ALS) and multiple sclerosis are adult-onset neurological diseases that have distinct pathological manifestations. However, evidence indicates that these conditions share a common link with copper dysregulation, with prior research showing decreased copper levels in spinal cord gray matter and elevated copper levels in white matter areas associated with pathology in both conditions.
Meanwhile, metallothionein-3 (MT3), a key copper metabolism regulator in the central nervous system, has been recognized as an important target for ALS and MS research, though research on its link to these conditions is limited.
In a study published in Nature, Adam P. Gunn, BSc, PhD, of the University of Melbourne in Australia, and colleagues examined the relationship between copper and MT3 in the ALS and MS spinal cord. Using quantitative mass spectrometry approaches, the researchers found that protein levels of MT3 were significantly lower in the ALS (32%, P=0.015) and MS (36%, P=0.003) spinal cords compared with controls.
Similar alterations were not observed when measuring other MT isoforms, including MT1 and MT2, suggesting that this change is selective to MT3. In addition, immunohistochemical assessment of ALS and MS lumbar spinal cord sections showed that MT3 staining was weaker in ALS and MS spinal cords compared with controls, particularly in gray matter. The observed decrease in MT3 was correlated with levels of copper and MT3-copper binding.
Overall, these findings support prior research showing that copper dysregulation is a shared feature of ALS and MS, with decreased levels of copper occurring alongside decreased MT3 expression in both conditions. The researchers noted that further research is needed to better understand the role of these changes in ALS and MS, which could help develop targeted therapies to treat both conditions.