DSD-1-Proteoglycan/Phosphacan and Receptor Protein Tyrosine Phosphatase-Beta Isoforms During Development and Regeneration of Neural Tissues

Andreas Faissner, Nicolas Heck, Alexandre Dobbertin and Jeremy Garwood

Interactions between neurons and glial cells play important roles in regulating key events of development and regeneration of the CNS. Thus, migrating neurons are partly guided by radial glia to their target, and glial scaffolds direct the growth and directional choice of advancing axons, e.g., a...

Excitatory Amino Acid Neurotoxicity

Thomas Gillessen, Samantha L. Budd and Stuart A. Lipton

The excitatory potency of the acidic amino acids glutamate and aspartate in various regions of the central nervous system (CNS) has been recognized since the 1960's.^1,2 Nevertheless, the earlier findings that these amino acids are (1) constituents of intermediary metabolism an...

Fibroblast Growth Factors

Christian Alzheimer and Sabine Werner

The FGFs comprise a large group of structurally similar polypeptide mitogens which currently includes 22 different members. The first members of this family, FGF1 (acidic FGF, aFGF) and FGF2 (basic FGF, bFGF), were described in 1986 by Jaye et al¹ and Abraham et al.²

Folding and Misfolding of alpha-Synuclein

Parkinson’s disease (PD) is a multifactorial movement disorder, in which both genetic and especially environmental factors play important roles. Substantial evidence implicates the aggregation of alpha-synuclein as a critical factor in PD. Rare familial cases of PD are associated with the mutations ...

Functional Roles of APP Secretases

Cleavage of APP by α-, β and γ-secretases strikingly resembles regulated intramembrane proteolysis (RIP), which is normally employed to generate signaltransducing fragments from transmembrane proteins. Protein 'RIPping' is initiated by signals like ligand binding causin...

Gene Therapy for Parkinson’s Disease

Gene therapy of central nervous system diseases is a rapidly emerging field in neuroscience. Potential applications are not restricted to congenital single-gene disorders; gene therapy of acquired and chronic diseases may be envisaged as well. Considerable progress has recently been made in the unde...

Genetics of alpha-Synucleinopathy

The alpha-synuclein gene, SNCA, was the first to be identified as a causative factor in Parkinson’s disease.1 There has long been contention as to whether Parkinson’s disease, Parkinson’s disease with dementia, and dementia with Lewy bodies represent distinct disorders or a continuum of one. The gen...

Heat Shock Proteins and Neuroprotection

Midori A. Yenari

In response to many metabolic disturbances and injuries including stroke, neurodegenerative disease, epilepsy and trauma, the cell mounts a stress response with induction of a variety of proteins, most notably the 70 kD heat shock protein (Hsp70). The possibility that s...

Histochemical Properties of Intrastriatal Mesencephalic Grafts

Lazaros C. Triarhou

The rationale behind neural transplantation studies using the weaver mouse model has been to replace degenerated neurons that are lost in the neurogenetic disease by intracerebrally grafted fetal mesencephalic cells.¹ The cellular properties of dopaminergic grafts had been stu...

Idiopathic Parkinson’s Disease: Staging an alpha -Synucleinopathy with a Predictable Pathoanatomy

Idiopathic Parkinson’s disease (IPD) is a multisystemic synucleinopathy of the human nervous system with functional consequences and a diagnostic potential that extend beyond the nigrostriatal system. Intracerebrally, only a few predisposed types of nerve cells develop the inclusion body pathology t...

Interleukin-10 and Psoriasis

K. Asadullah, W. Sterry and H.D. Volk

Interleukin (IL)-10 is an important immunoregulatory cytokine. One of its main biological function seems to be the limitation and termination of inflammatory responses. Remarkably, a relative deficiency in IL-10 expression is found in psoriasis, a frequent inflammatory skin disease, characterized by...

Intracellular Ca²⁺ Handling

Rod J. Sayer

Intracellular Ca²⁺ is regulated within three major compartments: the cytosol, the endoplasmic reticulum and mitochondria. This Chapter reviews the mechanisms involved in handling of Ca²⁺ within these compartments with reference to potential strategies for neuroprote...

Introduction

Lazaros C. Triarhou

Dopamine and Parkinson's Disease

Movement control is accomplished by complex interactions among various groups of nerve cells in the central nervous system. One such important group ofneurons is located in the substantia nigra in the ventral midbrain. Nigral neurons give rise to an ...

Invasive Drug Delivery

Ulrike Blömer, Arnold Ganser and Michaela Scherr

The central nervous system is a very attractive target for new therapeutic strategies since many genes involved in neurological diseases are known and often only local low level gene expression is required. However, as the blood brain barrier on one hand prevents som...

Lesion-Induced Axonal Sprouting in the Central Nervous System

Thomas Deller, Carola A. Haas, Thomas M. Freiman, Amie Phinney, Mathias Jucker and Michael Frotscher

Injury or neuronal death often come about as a result of brain disorders. Inasmuch as the damaged nerve cells are interconnected via projections to other regions of the brain, such lesions lead to axonal loss in distal target areas. The central nervous system responds to deafferentation by mea...

Modulating Amyloid-β Levels by Immunotherapy: A Potential Therapeutic

Cynthia A. Lemere, Timothy J. Seabrook, Melitza Iglesias, Chica Mori, Jodi F. Leverone and Edward T. Spooner

Alzheimer's disease (AD) is the most common form of dementia and afflicts ~15-20 million people worldwide. Currently, there is no effective cure. Research efforts over the past decade have demonstrated that amyloid-beta protein (Aβ), a small peptide generated from its large precurso...

Molecular Biology of Parkin

The recent linkage of genetic mutations in the parkin gene to familial Parkinson’s disease (PD) and the seminal discovery that parkin functions as an ubiquitin ligase associated with the ubiquitin-proteasome system (UPS) have generated widespread interest among PD researchers directed at linking UPS...

Molecular Neuropathology: Novel Methods and Markers for the Detection of Modified a-Synuclein in Lewy Body Disorders

Soon after the discovery of point mutations in the α-synuclein (αSYN) gene as a rare cause of familial Parkinson’s disease, αSYN was identified as the major component of Lewy bodies (LBs) and Lewy neurites (LNs), the diagnostic hallmarks in Parkinson’s disease (PD) and dementia with L...

Neurochemical Indices of Functional Restoration

Lazaros C. Triarhou

A general asset of the weaver model is that one can study graft development at the same time as the animal's own dopamine (DA) system continues to undergo a progressive degeneration, which is reflected in the relatively slow loss of cells in the mutant, compared with the rapid and trauma...

Neuronal Survival and Cell Death Signaling Pathways

Richard S. Morrison, Yoshito Kinoshita, Mark D. Johnson, Saadi Ghatan, Joseph

Neuronal viability is maintained through a complex interacting network of signaling pathways that can be perturbed in response to a multitude of cellular stresses. A shift in the balance of signaling pathways after stress or in response to pathology can have drastic consequences for the ...

Neuroprotection by cAMP: Another Brick in the Wall

Mariana S. Silveira and Rafael Linden

Programmed cell death occurs in the nervous system both in normal development as well as in pathologic conditions, and is a key issue related to both brain repair and neurodegenerative diseases. Modulation of cell death in the nervous system may involve neurotrophic factors and other peptides, ne...

Neuroprotective Activity of Metabotropic Glutamate Receptor Ligands

Peter J. Flor, Giuseppe Battaglia, Ferdinando Nico

Metabotropic glutamate receptors form a family of currently eight subtypes (mGluR1 o -8), subdivided into three groups (I-III). Activation of group-II (mGluR2 and -3) or group-III metabotropic glutamate receptors (mGluR4, -6, -7 and -8) has been established to be neuroprotective in vitro...

Neuroprotective Strategies in Alzheimer's Disease

Christian Behl

Alzheimer's disease (AD) is a deadly progressive neurodegenerative disorder. Various aspects of the biochemistry of the AD-associated amyloid b protein (Ab) are well-described and understood. The deposition of A

Neuroprotective Strategies in Animal and in vitro-Models of Neuronal Damage: Ischemia and Stroke

Matthias Endres and Ulrich Dirnagl

Cell death following cerebral ischemia is mediated by a complex pathophysiologic interaction of different mechanisms. In this Chapter we will outline the basic principles as well as introduce in vitro and in vivo models of cerebral ischemia. Mechanistically, excitotoxic...

Neurotrophins

Georg Dechan and Harald Neumann

Nerve growth factor was the first identified protein with anti-apoptotic activity on neurons. This prototypic neurotrophic factor, together with the three structurally and functionally related growth factors brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT3) and neurotro...