Manganese and Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by loss of upper and lower motor neurons and sclerosis of motor pathways in the spinal cord, leading to widespread progressive skeletal muscle atrophy. ALS is typically fatal within 2–5 years of symptom onset. The incidence of ALS is largely uniform across most parts of the world.

Mn is an essential ubiquitous trace element required for normal growth, development and cellular homeostasis.

Mn functions as a required cofactor of several enzymes necessary for neuronal and glial cell function, as well as enzymes involved in neurotransmitter synthesis and metabolism.

Manganese crosses barrier systems at the choroid plexus and accumulates in the central nervous system, with a longer half-life in nervous tissue. Manganese (Mn) has been specifically implicated in ALS pathogenesis.

Mn levels in brain tissue average approximately 1–2 µg/g dry weight. The concentration of Mn in the brain varies across brain regions under excessive exposures. In the ALS, Mn contents were higher in the anterior horn and lateral fasciculus than in the posterior horn.

Mn overload has also been implicated in ALS. This link was first described by Voss, who documented a Mn smelter who developed occupational manganism and bulbar ALS in Germany
Manganese and Amyotrophic Lateral Sclerosis