Gliopathies

Gliopathies are diseases in which glial cells—the non-neuronal cells that support and insulate neurons—are the primary site of pathology. In the central nervous system, glial cells include astrocytes, oligodendrocytes, and microglia; in the peripheral nervous system, Schwann cells perform a similar support role. When glial cells are dysfunctional, neuronal function can be secondarily affected, leading to developmental abnormalities, demyelination, neuroinflammation, or neurodegeneration. Gliopathies can be genetic or acquired and may involve the CNS, the PNS, or both.

Astrocyte-related gliopathies include conditions where astrocyte dysfunction disrupts brain homeostasis. Alexander disease, caused by mutations in GFAP, is a well-known example. Vanishing white matter disease involves mutations in eIF2B and features widespread white matter injury with astrocyte and oligodendrocyte involvement. Astrocyte pathology can disturb ion and water balance, metabolic support, and the blood-brain barrier, contributing to gliosis and neuron vulnerability.

Oligodendrocyte- and myelin-related gliopathies primarily affect myelination. Pelizaeus-Merzbacher disease, due to PLP1 mutations, is a prototypical hypomyelinating leukodystrophy. Other disorders of oligodendrocyte function or development also fall under this category, often presenting with motor impairment and white matter abnormalities on MRI.

Microglial and inflammatory gliopathies reflect the role of glial immune cells in disease. Abnormal microglial activation or microglial dysfunction can contribute to neuroinflammation and secondary damage to neurons and oligodendrocytes in various leukodystrophies and neurodegenerative conditions.

Diagnosis relies on clinical assessment, neuroimaging, and genetic testing. Treatment is largely supportive, with emerging approaches including gene therapies and targeted molecular therapies in research and clinical trials.