The field of neurotrophic factors has witnessed exp- sive growth in the past decade. As is usual in scientific in- vation, this progress has been closely associated with methodological advances. The introduction of molecular b- logical techniques into the neurotrophic factor field led to the discovery of new families of neurotrophic growth f- tors and their receptors. Production of growth factors by recombinant technology played a crucial part. The example of nerve growth factor, the paradigmatic neurotrophic factor, illustrates this point. A decade ago investigators were forced to purify small quantities of this protein from murine salivary glands, but much larger qu- tities of recombinant nerve growth factor are now available for experimentation as well as clinical development. A decade ago there was a controversy about the existence of nerve growth factor in the brain and the immunoassays used for its measurement, but current publications report the precise localization of gene expression for nerve growth factor and its receptor in the brain. Neurotrophic Factors aims at presenting the techniques that have been crucial to the realization of these rapid advances and thus have helped propel the neurotrophic factors field to its current status of high visibility. These techniques range from molecular biological methods used for cloning and production, to cell culture methods for assessing biological activities, to animal models of nervous system injury (nec- sary for the development of therapeutic agents from neurotrophic factors).

This volume contains the proceedings of the sixth Colloque M6decine et Re- cherche organized by the Fondation Ipsen pour la Recherche Therapeutique and devoted to Alzheimer's disease. It was held in Strasbourg on April 25, 1990 and dedicated to growth factors and Alzheimer's disease. The proceedings of the previous meetings were published as the present one in the same series: Immunology and Alzheimer's disease (A. Pouplard-Barthelaix, J. Emile, Y Christen eds., 1988), Genetics and Alzheimer's disease (P.-M. Sinet, Y Lamour, Y Christen eds., 1988), Neuronal grafting and Alzheimer's disease (F. Gage, A. Privat, Y Christen eds., 1989), Biological markers and Alzheimer's disease (F. Boller, R. Katzman, A. Rascol, J.-L. Signoret, Y Christen eds., 1989), Imaging, cerebral topography and Alzheimer's disease (S. I. Rapoport, H. Petit, D. Leys, Y Christen eds., 1990). The next meeting of the series entitled Neurophilosophy and Alzheimer's disease was being held in La Jolla (California, USA) on January 11,1991. The proceed- ings will be published this year. Yves Christen Fondation Ipsen Acknowledgements. The editors wish to express their gratitude to M. Sensenbren- ner (Strasbourg), A. Bjorklund (Lund), R. Terry (La Jolla) for their collaboration as chairmen for the meeting, G. Vincendon, dean of the Facult6 de M6decine de Strasbourg, who made the introductive talk, Mary Lynn Gage for her editorial assistance and Jacqueline Mervaillie for the organization of the meeting. Contents Neurotrophic Factors and Neurodegenerative Diseases F Hefti and B. Knusel ...

The pharmacology of neurotrophic factors is part of the general field called neuroprotection or neurodegeneration, which has emerged during the past two decades. This new broad research area has identified molecular mechanisms that regulate the morphological plasticity of the nervous system and, in con sequence, discovered novel pharmacological approaches to manipulate these processes in disease states. The new, structural neuropharmacology as de scribed in this volume attempts to regulate the anatomic aspects of the nervous system and is perhaps comparable to hardware manipulation in computer systems. In contrast, classical neuropharmacology identified multiple ways to modify the function of existing synapses or ion channels in the nervous system, comparable to software manipulations in the computer field. The pharmacol ogy of neurotrophic factor is at an early stage and has not produced any major drugs yet. However, the first quintessential clinical trials have been carried out in the past two years or are currently in progress. Rapid further advances can be expected. The discovery of nerve growth factor (NGF), the first protein known to promote survival and growth of nerve cells, led to the discovery of a family of related proteins, the neurotrophins and their receptors. This concept was generalized to incorporate many other protein families that are included in the functional definition of neurotrophic factors, i. e. , proteins able to regulate survival and differentiation of neurons.

In the past five years significant progress has been made in our basic and clinical under standing of Parkinson's disease. The discovery that MPTP, a relatively simple molecule, is able to induce parkinsonism in otherwise healthy adult humans, and the recent interest in the possibility of "transplantation" procedures as a therapeutic modality in the treatment of Parkin son's disease have generated enormous interest in research related to Parkinson's disease. In this setting, the National Parkinson Foundation decided to organize a research meeting to bring together scientists actively engaged in research relevant to the study of Parkinson's disease, to accelerate its progress and to promote an exchange of ideas. This meeting took place in Janu ary 1988 at Key Biscayne, Florida. It was decided to publish the proceedings ofthis meeting to allow rapid documentation of the participants current findings and views regarding this rapidly of this volume follows the organization of the meeting and begins evolving field. The structure with a clinical and neuropathological review of current knowledge regarding Parkinson's dis ease. Since dopaminergic neurons playa major role in the pathophysiology of the disease, many of the contributions relate to some aspects of dopaminergic function including localiza tion, regulation, and pharmacology of dopamine receptors. A special effort has been made to provide a summary of the present knowledge of the cellular biology of the dopaminergic neurons."

The field of neurotrophic factors has witnessed exp- sive growth in the past decade. As is usual in scientific in- vation, this progress has been closely associated with methodological advances. The introduction of molecular b- logical techniques into the neurotrophic factor field led to the discovery of new families of neurotrophic growth f- tors and their receptors. Production of growth factors by recombinant technology played a crucial part. The example of nerve growth factor, the paradigmatic neurotrophic factor, illustrates this point. A decade ago investigators were forced to purify small quantities of this protein from murine salivary glands, but much larger qu- tities of recombinant nerve growth factor are now available for experimentation as well as clinical development. A decade ago there was a controversy about the existence of nerve growth factor in the brain and the immunoassays used for its measurement, but current publications report the precise localization of gene expression for nerve growth factor and its receptor in the brain. Neurotrophic Factors aims at presenting the techniques that have been crucial to the realization of these rapid advances and thus have helped propel the neurotrophic factors field to its current status of high visibility. These techniques range from molecular biological methods used for cloning and production, to cell culture methods for assessing biological activities, to animal models of nervous system injury (nec- sary for the development of therapeutic agents from neurotrophic factors).

In the past five years significant progress has been made in our basic and clinical under- standing of Parkinson's disease. The discovery that MPTP, a relatively simple molecule, is able to induce parkinsonism in otherwise healthy adult humans, and the recent interest in the possibility of "transplantation" procedures as a therapeutic modality in the treatment of Parkin- son's disease have generated enormous interest in research related to Parkinson's disease. In this setting, the National Parkinson Foundation decided to organize a research meeting to bring together scientists actively engaged in research relevant to the study of Parkinson's disease, to accelerate its progress and to promote an exchange of ideas. This meeting took place in Janu- ary 1988 at Key Biscayne, Florida. It was decided to publish the proceedings ofthis meeting to allow rapid documentation of the participants current findings and views regarding this rapidly of this volume follows the organization of the meeting and begins evolving field. The structure with a clinical and neuropathological review of current knowledge regarding Parkinson's dis- ease. Since dopaminergic neurons playa major role in the pathophysiology of the disease, many of the contributions relate to some aspects of dopaminergic function including localiza- tion, regulation, and pharmacology of dopamine receptors. A special effort has been made to provide a summary of the present knowledge of the cellular biology of the dopaminergic neurons.