Dysfunctions in brain
cholesterol homeostasis have been extensively related to
brain disorders. The major elimination pathway of brain
cholesterol is its hydroxylation into 24 (S)-hydroxycholesterol by the
cholesterol 24-hydroxylase (
CYP46A1). Interestingly, there seems to be an association between
CYP46A1 and high-order brain functions, in a sense that increased expression of this
hydroxylase improves cognition, while a reduction leads to a poor cognitive performance. Moreover, increasing amount of epidemiological, biochemical and molecular evidence, suggests that
CYP46A1 has a role in the pathogenesis or progression of
neurodegenerative disorders, in which up-regulation of this
enzyme is clearly beneficial. However, the mechanisms underlying these effects are poorly understood, which highlights the importance of studies that further explore the role of
CYP46A1 in the central nervous system. In this review we summarize the major findings regarding
CYP46A1, and highlight the several recently described pathways modulated by this
enzyme from a physiological and pathological perspective, which might account for novel therapeutic strategies for
neurodegenerative disorders.