Journal of Neurochemistry

Tetrahydrobiopterin (BH4) is an essential cofactor of tyrosine hydroxylase (TH). We found that BH4 and dopa administration in infancy restored the loss of TH protein caused by BH4 deficiency and that the effects of these treatments are attenuated in young adulthood. These findings indicate that the post-natal augmentation of TH protein requires catecholamines and suggest that there is a critical period for the dopaminergic development.

The α2-Antiplasmin (α2AP) protein regulates cellular functions independently or dependently of plasmin, and is highly expressed in the hippocampus. However, the role of α2AP was unclear. Here, we first report that α2AP induces dendritic growth in hippocampal neurons through p38 MAPK activation, independent of plasmin, providing new insights into the role of α2AP in the CNS.

We report here that nanomolar Aβ can induce neuronal loss in culture by activating microglia to release MFG-E8 (Milk-fat globule-EGF factor 8 protein), which binds and opsonizes neurons for phagocytosis by microglia, thereby killing the neurons by phagoptosis. The essential role of MFG-E8 in Aβ-induced phagoptosis, suggests this bridging protein as a potential therapeutic target for Alzheimer's and other neurological diseases involving inflammatory neuronal loss.

We show that the mood-stabilizing drugs, valproic acid (VPA) and Li⁺, could up-regulate FGF-1B promoter through inhibition of HDACs and GSK-3. We further demonstrate that treatment of VPA increases histone acetylation around the regulatory region (18-bp cis-element) of FGF-1B promoter. Importantly, VPA could induce more neuronal differentiation in FGF-1B positive neural stem/progenitor cells than FGF-1B negative cells.