Early Mitochondrial Dysfunction and Myelin Loss Key Factors in Multiple Sclerosis Brain Damage

Multiple sclerosis (MS) affects approximately 2.3 million individuals worldwide. A significant proportion, around 80%, exhibit inflammation within the cerebellum, the brain region crucial for movement and balance regulation. This inflammation can result in symptoms like tremors, impaired coordination, and motor control difficulties, which tend to persist and progressively worsen as the cerebellum undergoes tissue degeneration.

Recent research conducted by the University of California, Riverside, provides new insights into the mechanisms driving cerebellar degeneration in MS. The study highlights that mitochondrial dysfunction—a disruption in the energy-producing components within cells—may play a pivotal role in neuronal loss, specifically targeting Purkinje cells that are vital for motor coordination. The researchers observed a marked decrease in the mitochondrial protein COXIV in demyelinated Purkinje cells, indicating impaired mitochondrial activity directly contributing to cell death and weakening of cerebellar structures.

The study emphasizes the importance of Purkinje cells in orchestrating smooth and coordinated movements. Damage and loss of these cells lead to ataxia, a condition characterized by lack of muscle control and balance issues. The researchers found that in MS, these neurons exhibit structural shrinkage, loss of myelin—an insulating layer surrounding nerve fibers—and mitochondrial dysfunction, all of which impair their energy supply and lead to cell deterioration.

Using a mouse model known as experimental autoimmune encephalomyelitis (EAE), which mimics MS symptoms, the researchers observed similar patterns of Purkinje cell loss and mitochondrial impairment over time. Early in the disease, mitochondrial failure occurs alongside myelin degradation, suggesting that energy deficits within neurons precede cell death and contribute significantly to disease progression.

This research highlights that mitochondrial health is integral to preventing neuronal damage in MS. It also underscores the potential for therapies aimed at preserving mitochondrial function, which could slow or halt neurological decline. The investigators plan to further explore how different types of brain cells, such as oligodendrocytes responsible for myelin production and supportive astrocytes, are affected by mitochondrial impairment in MS.

By analyzing postmortem cerebellar tissue from MS patients and healthy controls, the team aims to develop targeted strategies to protect brain cells from early degenerative changes. Ultimately, improving our understanding of mitochondrial roles in neurodegeneration could lead to innovative treatments to preserve movement and balance functions in individuals with MS.