A new study suggests mitochondrial dysfunction may play a key role in the progressive loss of neuronal cells, called Purkinje cells, and worsening motor impairments in multiple sclerosis.

MS is marked by chronic inflammation and demyelination in the central nervous system. Demyelination is the process in which the myelin sheath — a protective, insulating layer surrounding nerve fibers in the brain and spinal cord — is damaged or lost. This disruption interferes with the normal transmission of electrical signals along the nerves, resulting in various neurological issues. Mitochondria are vital structures within cells that generate most of the cell’s energy, earning them the nickname “powerhouses” of the cell.

The study by University of California, Riverside proposed inflammation and demyelination in the cerebellum disrupt mitochondrial function, contributing to nerve damage and Purkinje cell loss. The researchers observed a significant loss of a mitochondrial protein in demyelinated Purkinje cells, suggesting that mitochondrial impairment contributes directly to cell death and cerebellar damage.

Purkinje cells

When walking or moving, many parts of the brain and body work together — our muscles, spine, eyes, ears, and especially our brain. A key brain area for movement and balance is the cerebellum. Inside the cerebellum are special cells called Purkinje neurons. These large, highly active cells help coordinate smooth, precise movements — such as dancing, throwing a ball, or even walking. They’re essential for balance and fine motor skills. In diseases such as MS, the cerebellum can be damaged, and Purkinje cells often begin to die. This leads to problems with coordination and movement, a condition known as ataxia.

The researchers looked at brain tissue from MS patients and found the neurons had fewer branches, were losing myelin, and had mitochondrial problems — meaning their energy supply was failing. Because Purkinje cells play such a central role in movement, their loss can cause serious mobility issues. Understanding why they’re damaged in MS could help us find better treatments to protect movement and balance in people with the disease.

Powering down

The research team also used a well-established mouse model known as experimental autoimmune encephalomyelitis — a mouse model that develops MS-like symptoms — to investigate mitochondrial alterations during disease progression. The researchers found that the EAE mice lost Purkinje cells over time, just like people with MS did. Although the mouse model does not capture every aspect of MS, its similarities to human disease make it a valuable tool for studying neurodegeneration and testing potential therapies.

The researchers said the findings offer critical insights into the progression of cerebellar dysfunction in MS. Targeting mitochondrial health may represent a promising strategy to slow or prevent neurological decline and improve quality of life for people living with MS. These findings bring researchers closer to understanding the complex mechanisms of MS and developing more effective, targeted treatments for this debilitating disease.

Next, the team will investigate whether the mitochondrial impairment found in Purkinje cells also affects other brain cells such as oligodendrocytes, which help form white matter, or astrocytes, which support overall brain function.

The findings were published in the Proceedings of the National Academy of Sciences.