Cerebellum in neurodegenerative diseases: Advances, challenges, and prospects

Abstract

Neurodegenerative diseases (NDs) are a group of neurological disorders characterized by the progressive dysfunction of neurons and glial cells, leading to their structural and functional degradation in the central and/or peripheral nervous system. Historically, research on NDs has primarily focused on the brain, brain stem, or spinal cord associated with disease-related symptoms, often overlooking the role of the cerebellum. However, an increasing body of clinical and biological evidence suggests a significant connection between the cerebellum and NDs. In several NDs, cerebellar pathology and biochemical changes may start in the early disease stages. This article provides a comprehensive update on the involvement of the cerebellum in the clinical features and pathogenesis of multiple NDs, suggesting that the cerebellum is involved in the onset and progression of NDs through various mechanisms, including specific neurodegeneration, neuroinflammation, abnormal mitochondrial function, and altered metabolism. Additionally, this review highlights the significant therapeutic potential of cerebellum-related treatments for NDs.