Alzheimer's Disease

187 Pages·2008·3.5 MB·English

by  Michael A. Brodney (auth.), Michael A. Brodney (eds.)

2
Topics in Medicinal Chemistry
Editorial Board:
P. R. Bernstein · A. Buschauer · J. A. Lowe · H. U. Stilz
Alzheimer’s Disease
Volume Editors: Lit-Fui Lau · Michael A. Brodney
With contributions by
S. Berg · R. V. Bhat · M. A. Brodney · J. Burrows · A. I. Bush
G. Grossberg · L.-F. Lau · J. Lindquist · Q. Jiang · J. Kao · G. Landreth
S. Mandrekar · H. D. Soares · D. L. Sparks · A. R. White
123
Drug research requires interdisciplinary team-work at the interface between chemistry, biology and
medicine. Therefore, the new topic-related series should cover all relevant aspects of drug research,
e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural
biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry includ-
ing combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening,
pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level,
structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology
and pharmacogenomics.
In references Topics in Medicinal Chemistry is abbreviated Top Med Chem and is cited as a journal.
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Library of Congress Control Number: 2007935106
ISSN 1862-2461
ISBN 978-3-540-74228-9 Springer Berlin Heidelberg New York
DOI 10.1007/978-3-540-74229-6
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Volume Editors
Dr. Lit-Fui Lau Dr. Michael A. Brodney
CNS Discovery CNS Discovery
Pfizer Global Research & Development Pfizer Global Research & Development
Groton, CT 06340 Groton, CT 06340
USA USA
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Preface to the Series
Medicinal chemistry isbothscienceandart.Thescienceofmedicinal chemistry
offers mankind one of its best hopes for improving the quality of life. The art
of medicinal chemistry continues to challenge its practitioners with the need
for both intuition and experience to discover new drugs. Hence sharing the
experience of drug discovery is uniquely beneficial to the field of medicinal
chemistry.
The series Topics in Medicinal Chemistry is designed to help both novice
and experienced medicinal chemists share insights from the drug discovery
process. For the novice, the introductory chapter to each volume provides
background and valuable perspective on a field of medicinal chemistry not
available elsewhere. Succeeding chapters then provide examples of successful
drug discovery efforts that describe the most up-to-date work from this field.
The editors have chosen topics from both important therapeutic areas and
from work that advances the discipline of medicinal chemistry. For exam-
ple, cancer, metabolic syndrome and Alzheimer’s disease are fields in which
academia and industry are heavily invested to discover new drugs because of
their considerable unmet medical need. The editors have therefore prioritized
covering new developments in medicinal chemistry in these fields. In addition,
important advances in the discipline, such as fragment-based drug design and
other aspects of new lead-seeking approaches, are also planned for early vol-
umes in this series. Each volume thus offers a unique opportunity to capture
the most up-to-date perspective in an area of medicinal chemistry.
Dr. Peter R. Bernstein
Prof. Dr. Armin Buschauer
Dr. John Lowe
Dr. Hans Ulrich Stilz
Preface to Volume 2
It was one hundred and one years ago that Alois Alzheimer presented at a sci-
entific meeting a case of progressive dementia in a 51-year-old patient Auguste
D. Postmortem analysis revealed two pathologies, namely, senile plaques and
neurofibrillary tangles. These findings were published the following year in
1907. In 1910 Emil Kraepelin, Alzheimer’s mentor, named this disease after
its discoverer. The two initial pathological findings remain the postmortem
diagnostic features of Alzheimer’s disease (AD) today. At the time, however,
Kraepelin made the distinction between AD and senile dementia (> 65 years
old) despite their similarities in pathologies and clinical symptoms [1, 2]. In
1976 Robert Katzman argued in an editorial in the April issue of Archives
of Neurology that this distinction be removed. AD has thus morphed from
a rare orphan disease to one with a much bigger socioeconomic threat. This
nosological shift has brought AD into the lime light and exponentially—and
thankfully—hastened the pace of research. Enormous strides have been made
in understanding the root causes and risk factors of the disease. Analogous to
the discovery of new cancer treatments over the past 20 years (see Volume 1),
advances in understanding the underlying molecular biology are providing
novel drug targets for future research. These efforts have resulted in greater
than 500 ongoing clinical trials focused on novel mechanisms and interven-
tion points in the disease. These trials will hopefully lead to the first approval
of a disease-modifying agent for AD and pave the way for an arsenal of new
medications.
October, 2007, Groton Lit-Fui Lau and Michael A. Brodney
Connecticut, USA
1. Ballenger JF (2006) J Alzheimers Dis 9:5
2. Lage JM (2006) J Alzheimers Dis 9:15
Contents
Therapeutic Approaches for the Treatment of Alzheimer’s Disease:
An Overview
L.-F. Lau · M. A. Brodney . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Cholinesterase Inhibitors
J. Kao · G. Grossberg . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Beyond Cholesterol: Statin Benefits in Alzheimer’s Disease
H. D. Soares · D. L. Sparks . . . . . . . . . . . . . . . . . . . . . . . . . 53
PPARγ Agonists for the Treatment of Alzheimer’s Disease
Q. Jiang · S. Mandrekar · G. Landreth . . . . . . . . . . . . . . . . . . . 81
Metal Complexing Agents for the Treatment of Alzheimer’s Disease
A. R. White · A. I. Bush . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
GSK-3 Inhibitors for the Treatment of Alzheimer’s Disease
R. V. Bhat · S. Berg · J. Burrows · J. Lindquist . . . . . . . . . . . . . . . 137
Author Index Volumes 1–2 . . . . . . . . . . . . . . . . . . . . . . . . . 175
Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
Top Med Chem (2008) 2: 1–24
DOI 10.1007/7355_2007_017
 Springer-Verlag Berlin Heidelberg
Published online: 30 November 2007
Therapeutic Approaches
for the Treatment of Alzheimer’s Disease: An Overview
Lit-Fui Lau (✉) · Michael A. Brodney (✉)
CNS Discovery, Pfizer Global Research and Development, Groton, CT 06340, USA