Multiple sclerosis (MS) affects about 2.3 million people worldwide. In roughly 80% of cases, the disease involves inflammation in the cerebellum, a region of the brain essential for balance and coordinated movement. Damage in this area can trigger tremors, unsteady motion, and difficulty controlling muscles. Over time, these symptoms often intensify as healthy tissue in the cerebellum is gradually lost.

New research from the University of California, Riverside offers fresh insight into why this decline occurs. The study, published in the Proceedings of the National Academy of Sciences, points to malfunctioning mitochondria as a major contributor to the progressive breakdown of cerebellar neurons known as Purkinje cells. The loss of these cells appears closely tied to worsening movement problems in people with MS.

Inflammation, Myelin Loss, and Energy Failure

MS is defined by ongoing inflammation and demyelination within 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 destroyed. Without this insulation, electrical signals struggle to travel efficiently along nerves, leading to a wide range of neurological symptoms.

Mitochondria play a different but equally critical role. These structures supply most of a cell's energy, which is why they are often called the "powerhouses" of the cell.

"Our study, conducted by my graduate student Kelley Atkinson, proposes that inflammation and demyelination in the cerebellum disrupt mitochondrial function, contributing to nerve damage and Purkinje cell loss," said Seema Tiwari-Woodruff, a professor of biomedical sciences in the UC Riverside School of Medicine, who led the research team. "We observed a significant loss of the mitochondrial protein COXIV in demyelinated Purkinje cells, suggesting that mitochondrial impairment contributes directly to cell death and cerebellar damage."

Why Purkinje Cells Matter

Everyday movements such as walking, reaching, or maintaining balance rely on tight coordination between muscles, sensory organs, and multiple brain regions. The cerebellum plays a central role in this process.

"Inside the cerebellum are special cells called Purkinje neurons," Tiwari-Woodruff said. "These large, highly active cells help coordinate smooth, precise movements -- like dancing, throwing a ball, or even just walking. They're essential for balance and fine motor skills."

In MS and related neurological diseases, damage to the cerebellum often leads to the gradual death of Purkinje cells. As these neurons disappear, people may develop ataxia, a condition marked by poor coordination and unstable movement.

"Our research looked at brain tissue from MS patients and found major issues in these neurons: they had fewer branches, were losing myelin, and had mitochondrial problems -- meaning their energy supply was failing," Tiwari-Woodruff said. "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."