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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 ...
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 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.
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.
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