Manganese Neurotoxicity: A Comprehensive Review of Pathophysiology and Inherited and Acquired Disorders

Area of Science:

• Biochemistry
• Neuroscience
• Genetics

Background:

• Manganese (Mn) is an essential trace element crucial for enzyme function, including antioxidant defense via mitochondrial superoxide dismutase.
• Chronic manganese overexposure leads to manganism, a neurological disorder with Parkinson's-like symptoms.
• Mn homeostasis is tightly regulated by various uptake and efflux transporters.

Purpose of the Study:

• To review known manganese transporters and their role in neurotoxicity.
• To provide an overview of inherited and acquired disorders of manganese metabolism.
• To discuss current treatment strategies for manganese-related disorders.

Main Methods:

• Literature review of manganese transporters, neurotoxicity, and metabolic disorders.
• Analysis of genetic mutations (SLC30A10, SLC39A14) linked to inherited manganese metabolism disorders.
• Synthesis of clinical presentations and associated features (dystonia, parkinsonism, liver disease, polycythemia).

Main Results:

• Specific transporters (SLC30A10, SLC39A14) are critical in inherited manganese metabolism disorders.
• Early diagnosis and treatment of these inherited disorders significantly improve prognosis.
• Clinical features like dystonia, parkinsonism, liver disease, and polycythemia can indicate specific genetic mutations.

Conclusions:

• Familiarity with manganese transporters and associated clinical presentations is essential for physicians.
• Prompt identification of inherited manganese metabolism disorders, particularly those involving SLC30A10 and SLC39A14, is crucial for effective management.
• This review consolidates knowledge on manganese transport, toxicity, and metabolic disorders, aiding clinical practice and research.