Table Of ContentHandbook of
Experimental Pharmacology
Volume 155
Editorial Board
G.Y.R. Born, London
M. Eichelbaum, Stuttgart
D. Ganten, Berlin
H. Herken, Berlin
F. Hofmann, Munchen
L. Limbird, Nashville, TN
W. Rosenthal, Berlin
G. Rubanyi, Richmond, CA
K. Starke, Freiburg i. Br.
Springer-Verlag Berlin Heidelberg GmbH
eNS N europrotection
Contributors
M.E Beal, K.I Becker,A. Blesch, D.W. Choi, T.M. Dawson,
Y.L. Dawson, H.I Federoff, G.Z. Feuerstein,A.C. Foster,
S. Gandy, M.P. Goldberg, 1M. Hallenbeck, M.W. Halterman,
M. Jackson, G.A. Kerchner,A.H. Kim, W. Koroshetz,
M.P. Mattson, L.P. Miller, IW. Phillis, R.M. Poole, H.D. Rosas,
ID. Rothstein, M. Sasaki, c.P. Taylor, M.H. Tuszynski,
K.K.W. Wang, X. Wang, IB. Wiesner
Editors
Frank W. Marcoux and Dennis W. Choi
Springer
Dr. FRANK W. MARCOUX
Vice President, Biology,
Pfizer Global Research and Development
Ann Arbor Laboratories
2800 Plymouth Road
Ann Arbor, MI 48105
USA
e-mail:
Preface
"CNS neuroprotection" was a common subject of papers, symposia, and
reviews during the previous "decade of the brain." Indeed, in recent years,
experimental study of putative neuroprotective agents prompted clinical trials
of numerous drug candidates in acute and chronic human neurodegenerative
conditions. While the outcomes of these trials have not been as successful as
initially hoped, these were early explorations, and the pipeline of relevant
ideas continues to grow in strength and depth. We predict that early in this
new millennium, crippling disorders such as stroke and Alzheimer's disease
will be treated effectively by therapeutic neuroprotective strategies.
This volume of the Handbook of Experimental Pharmacology titled eNS
Neuroprotection provides a pharmacological perspective on currently promis-
ing neuroprotective approaches, and a clinical perspective on the challenges
involved in establishing the efficacy of these approaches through appropriate
clinical trials.
Section I, "Mechanistic Approaches to CNS Neuroprotection," reviews
major injury mechanisms that have formed the basis for many past and present
clinical trials conducted around the world. Dr. KIM and colleagues, Washington
University School of Medicine, review the status of blocking excitotoxicity as
an approach to CNS neuroprotection. Dr. WANG, Pfizer Global Research and
Development,Ann Arbor Laboratories, outlines evidence supporting a contri-
bution of apoptosis to pathological neuronal or glial cell loss. Drs. BECKER and
HALLENBECK, University of Washington and the National Institute on Neuro-
logical Diseases and Stroke, respectively, argue that inhibiting inflammatory
pathways in the brain can be neuroprotective. Dr. BEAL, Cornell University,
reviews mitochondria-directed approaches to neuroprotection. Dr. MATISON,
National Institute on Aging, summarizes the current understanding of how
disturbances in calcium homeostasis and intracellular signaling pathways par-
ticipate in neurodegeneration; Dr. SASAKI and colleagues, lohns Hopkins Uni-
versity, discuss the neuroprotective effects cif inhibiting nitric oxide toxicity.
Taken together, the chapters in Sect. I provide expert commentary on well-
studied mechanistic approaches to CNS neuroprotection.
Section II, "Neuroprotective Agents," reviews specific pharmacological
strategies for CNS neuroprotection. Dr. FOSTER and colleagues, Neurocrine
VI Preface
Biosciences, review adenosine-related approaches to neuroprotection. Dr.
TAYLOR, Pfizer Global Research and Development, Ann Arbor Laboratories,
argues that sodium and calcium ion channels are targets for neuroprotective
drugs. Dr. PHILLIS, Wayne State University, reviews the status of free radical
scavengers and other antioxidants as neuroprotective agents; and Drs.
FEUERSTEIN and WANG, DuPont Pharmaceuticals, discuss ways of manipulat-
ing chemokines and chemokine receptors to reduce neurodegeneration. The
chapters in Sect. II cover specific molecular targets for neuroprotection and
provide examples of pharmacological agents of current interest.
Section III, "CNS Delivery of Neuroprotective Therapies," highlights
gene-based neuroprotection strategies. Drs. BLESCH and TUSZYNSKI, Univer-
sity of California at San Diego, review ex vivo approaches to delivering new
genes to the CNS. Drs. HALTERMAN and FEDEROFF, University of Rochester,
discuss viral vector-based neuroprotective approaches.
Section IV, "Disease Targeting of Neuroprotective Therapies," presents
clinical perspectives on bringing neuroprotective approaches to bear upon
specific neurological disorders. Dr. GOLDBERG, Washington University, sum-
marizes some of the progress and challenges in developing neuroprotective
drugs to treat stroke. Dr. POOLE, Pfizer Global Research and Development,
Ann Arbor Laboratories, discusses approaches to neuroprotective therapy
in the traumatically injured CNS. Dr. GANDY, New York University, discusses
using neuroprotective approaches to treat patients with Alzheimer's disease;
Drs. JACKSON and ROTHSTEIN, Johns Hopkins University, do the same for
patients with amyotrophic lateral sclerosis; while Drs. ROSAS and KOROSHETZ,
Massachusetts General Hospital, focus on patients with Huntington's disease.
Taken together, these chapters yield insights into present and future opportu-
nities for neuroprotective therapies in specific neurodegenerative conditions.
eNS Neuroprotection provides a pharmacological view of neuroprotective
therapies. It is not intended to be exhaustive, but rather highlights major
mechanistic targets and therapeutic approaches, as well as related challenges
and opportunities in the clinic. The editors wish to thank all of the authors for
their excellent contributions to this volume and, moreover, to this rapidly
developing area of pharmacological research.
FRANK W. MARCOUX
DENNIS W. CHOI
List of Contributors
BEAL, M.E, Department of Neurology, Cornell University Medical College,
525 East 68th Street, New York, NY 10021, USA
e-mail:
VIII List of Contributors
FOSTER, A.C., Neurocrine Biosciences Inc., Department of Neuroscience,
10555 Science Center Drive, San Diego, CA 92121, USA
e-mail:
List of Contributors IX
PHILLIS, IW., Department of Physiology, Wayne State University School of
Medicine, 540 E. Canfield, Detroit, MI 48201, USA
e-mail:
