The extracellular‐signal regulated kinases 1/2 (ERK or ERKs) are involved in the regulation of important neuronal functions, including neuronal plasticity in normal and pathological conditions. We present findings that support the notion that the kinetics and localization of ERK are intrinsically linked, in that the duration of ERK activation dictates its subcellular compartmentalization and/or trafficking. The latter, in turn, dictates whether ERK‐expressing cells would enter a program of cell death, survival or differentiation. We summarize experimental data showing that chronic activation (...) of ERK plays a role in the mechanisms that trigger neurodegeneration. We also discuss how MKPs, members of the subclass of dual specificity phosphatases, might be the link between ERK kinetics and its subcellular localization. BioEssays 25:1085–1095, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

The discovery of neurogenesis and neural stem cells (NSC) in the adult CNS has overturned a long‐standing and deep‐routed “dogma” in neuroscience, established at the beginning of the 20th century. This dogma lasted for almost 90 years and died hard when NSC were finally isolated from the adult mouse brain. The scepticism in accepting adult neurogenesis has now turned into a rush to find applications to alleviate or cure the devastating diseases that affect the CNS. Here we highlight a number (...) of methodological, technical and conceptual drawbacks responsible for the historical denial of adult neurogenesis. Furthermore, we discuss old and new issues that need to be faced before NSC or endogenous neurogenesis can safely enter into the doctor's bag for therapies. BioEssays 30:135–145, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

In the mammalian brain dopamine systems play a central role in the control of movement, hormone release, emotional balance and reward. Alteration of dopaminergic neurotransmission is involved in Parkinson's disease and other movement disorders, as well as in some psychotic syndromes. This review summarises recent findings, which shed some light on signals and cellular interactions involved in the specification and maturation of the dopaminergic function during neurogenesis. In particular we will focus on three major issues: (1) the differentiation of dopaminergic (...) neurones triggered by direct contact with the midbrain floor plate cells through the action of sonic hedgehog; (2) the neurotrophic factors acting on dopaminergic neurones; and (3) the role of target striatal cells on the survival and the axonal growth of developing or grafted dopaminergic neurones. (shrink)