Regeneration of Degenerated Brain: A Promising Therapeutic Target Check Access

Neurogenesis in the brain is a lifelong process taking place primarily in the subgranular zone (SGZ) of the dentate gyrus of the hippocampus and the granular layer of the subventricular zone. Alzheimer disease (AD) brain attempts unsuccessfully to regenerate itself by activating the dentate gyrus neurogenesis to make up for the hippocampal neuronal loss. However, while the AD brain is able to induce a certain level of neuronal proliferation, these new brain cells do not mature into functional neurons. One of the major causes of this failure of AD brain to regenerate itself is the dysregulation of the neurotrophic factors, especially in the hippocampus. The level of the mitogenic factor, fibroblast growth factor-2 (FGF-2), is more than two-fold upregulated in AD hippocampus. We have found that both ciliary neurotrophic factor (CNTF) and the antidementia drug Cerebrolysin®, a standardized proteolytic digest of porcine brain which contains, among others, active peptides of CNTF, glial-derived growth factor (GDNF), and insulin-like growth factors -1 and -2 (IGF-1, IGF-2), counteract the effect of elevated FGF-2, and induce neuronal commitment and maturation in rat adult hippocampal progenitors. Furthermore, when administered in vivo, Cerebrolysin® enhances the dentate gyrus neurogenesis and improves cognition in normal adult rats. Peptidergic drugs that can enhance neurogenic/neurotrophic activities and improve cognition represent a promising therapeutic approach for the treatment of AD and other learning and memory disorders.