Neuroprotective actions of cerebellar and pineal allopregnanolone on Purkinje cells

The brain produces steroids de novo from cholesterol, so-called "neurosteroids." The Purkinje cell, a cerebellar neuron, was discovered as a major site of the biosynthesis of neurosteroids including sex steroids, such as progesterone, from cholesterol in the brain. Allopregnanolone, a progesterone metabolite, is also synthesized in the cerebellum and acts on the Purkinje cell to prevent cell death of this neuron. Recently, the pineal gland was discovered as an important site of the biosynthesis of neurosteroids. Allopregnanolone, a major pineal neurosteroid, acts on the Purkinje cell for the survival of this neuron by suppressing the expression of caspase-3, a crucial mediator of apoptosis. This review summarizes the discovery of cerebellar and pineal allopregnanolone and its neuroprotective action on Purkinje cells.