Reelin is a neurodevelopmental protein important in adult synaptic plasticity and learning and memory. Recent evidence points to the importance for Reelin proteolysis in normal signaling and in cognitive function. Support for the dysfunction of Reelin proteolysis in neurodegeneration and cognitive dysfunction comes from postmortem analysis of Alzheimer's diseases (AD) tissues including cerebral...

Reelin is an extracellular protein that controls many aspects of pre- and postnatal brain development and function. The molecular mechanisms that mediate postnatal activities of Reelin are not well understood. Here, we first set out to express and purify the full length Reelin protein and a biologically active central fragment. Second, we investigated in detail the signal transduction mechanism...

Reelin regulates nervous system development and modulates synaptic plasticity in the adult brain. Several findings suggest that alterations in Reelin signaling may contribute to neuronal dysfunction associated with Alzheimer’s disease (AD). Cell surface receptors for Reelin, including integrins and very-low-density lipoprotein receptor/apolipoprotein E2 receptor, may be targets of amyloid(A ) p...

Reelin signaling through the low-density lipoprotein receptor family members, apoliproprotein E receptor 2 (apoER2) and very-low-density lipoprotein receptor (VLDLR), plays a pivotal role in dictating neuronal lamination during embryonic brain development. Recent evidence suggests that this signaling system also plays a role in the postnatal brain to modulate synaptic transmission, plasticity, ...

Reelin controls the migration of neurons and layer formation during brain development. However, recent studies have shown that disrupting Reelin function in the adult hippocampus induces repositioning of fully differentiated neurons, suggesting a stabilizing effect of Reelin on mature neuronal circuitry. Indeed, Reelin was recently found to stabilize the actin cytoskeleton by inducing cofilin p...

UNLABELLED Notch signaling plays a crucial role in adult brain function such as synaptic plasticity, memory and olfaction. Several reports suggest an involvement of this pathway in neurodegenerative dementia. Yet, to date, the mechanism underlying Notch activity in mature neurons remains unresolved. In this work, we investigate how Notch regulates synaptic potentiation and contributes to the es...

The reelin signaling protein and its downstream components have been associated with synaptic plasticity and neurotransmission. The reelin signaling pathway begins with the binding of reelin to the transmembrane lipoprotein receptor apolipoprotein E receptor 2 (ApoER2), which in turns induces the sequential cleavage of ApoER2 by the sequential action of α- and γ-secretases. Using conditional-kn...

............................................................................................................... vii Chapter 1: Introduction ........................................................................................ 1 Neurogenesis in the Adult Mammalian Brain ............................................. 1 The Role of Adult Neurogenesis ................................................

Introduction Reelin gene (RELN) codes a large extracellular matrix glycoprotein with serine protease activity and is implicated in the modulation of neuronal signaling, synaptic transmission and plasticity. The reelin plays a fundamental and pivotal role in the development of laminar structures and may be one of the loci contributing to the positive linkage between chromosome 7q and autistic di...