Motor neurone disease (MND) is caused by a combination of genetic, environmental, and lifestyle factors, though the exact cause remains unknown. The disease results from the progressive failure and death of motor neurons, which are nerve cells responsible for controlling muscles.

Key Causes and Contributing Factors:

• Genetic Factors: Around 5-15% of MND cases are familial (hereditary), caused by mutations in specific genes such as SOD1, TDP43, FUS, and C9orf72. These gene mutations disrupt normal cell function and survival, and can be passed from parents to children

• Sporadic Cases: The majority (85-95%) of MND cases are sporadic, meaning they occur without a clear family history. These cases are thought to arise from a complex interplay of multiple small genetic susceptibilities combined with environmental and lifestyle risk factors

• Environmental and Lifestyle Factors: Research has investigated links to exposure to viruses, toxins, chemicals (including agricultural pesticides and heavy metals), mechanical or electrical trauma, military service, and high levels of exercise. However, evidence remains inconclusive and no definitive environmental cause has been established

• Cellular Mechanisms: Dysfunction in motor neuron transport systems, accumulation of toxic waste products, mitochondrial abnormalities, and harmful changes in surrounding glial cells contribute to motor neuron degeneration

• DNA Damage: Abnormalities in proteins involved in DNA repair, such as TDP-43, are found in most MND patients, leading to accumulation of DNA damage in motor neurons

In summary, MND likely results from a combination of genetic predisposition and environmental/lifestyle triggers that together cause motor neuron damage and death. Current research continues to explore these factors to better understand the disease and develop treatments