Researchers Review Role of Manganese in Huntington’s Disease Development

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by Alice Melão |

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The chemical compound manganese (Mn) has been reported to take part in the underlying mechanism of Alzheimer’s disease. However, little is known about its involvement in the development of other neurodegenerative diseases.

In the study titled “Manganese in manganism, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and Batten disease: A narrative review,” published in Neurology India, researchers review the role of manganese in the development of several neurological disorders, including Huntington’s disease.

Excessive environmental contact to Mn can cause a neurological condition called manganism, which has symptoms similar to those seen in Parkinson’s disease. Exposure to manganese is most often work-related and happens by inhalation.

Huntington’s is caused by the accumulation and clustering of an abnormal version of the huntingtin protein. Despite the clear toxic role that mutant huntingtin has in neuronal cells, its normal function is still unknown.

A previous study showed that huntingtin may take part in manganese transport. Analysis of a Huntington’s cell line revealed that the cells had significantly lower levels of Mn than healthy cells. Its levels were also found to be reduced in the striatum — the brain region that is affected in Huntington’s — of mouse models of the disease.

More recently, a study published in the journal Metallomics suggested that the reduced transport of Mn could be a compensatory response to the underlying molecular mechanisms of Huntington’s.

Researchers at the Vanderbilt Brain Institute also recognized that a manganese-dependent signaling pathway was impaired in patients’ cells and mouse models of the disease. This finding further supports the hypothesis that manganese could have a potential role in the development of Huntington’s.

“Decreased cellular manganese in HD [Huntington’s disease] could explain at least some HD pathogenic mechanisms,” the researchers wrote in their report published in Human Molecular Genetics.

“Further, differential manganese nutritional status of patients could be an important modifier of disease progression, as manganese deficiency is known to change several mechanisms known to be dysfunctional in Huntington’s disease models,” they added.

The HTT gene mutation that provides instructions to the huntingtin protein is known to be responsible for about half of the variations seen by the onset of the disease. Although evidence has pointed out that Mn might take part in the development of Huntington’s, it is not yet clear if it is also involved in disease onset. Additional studies are warranted to address this hypothesis.