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This volume reviews the new potential treatments and research in
the area of Alzheimer's disease. Special attention is given to
international developments in all fields relevant to new drug
development. Topics discussed include: progress in the
international harmonization of drug development guidelines for
dementia drugs; bioethics and law; development of rating
instruments; behavioural treatments; and the activities of the
Reagan Foundation. The text integrates basic and clinical research
findings, and provides evaluation of new approaches to therapy by
world leaders in the field. The potential benefit for Alzheimer
patients and families resulting from these research programmes,
from molecular biology to clinical pharmacology, is reviewed and
evaluated.
The cholinergic system has been recognized as playing an important
role not only in several forms of dementia besides Alzheimer's
Disease, but also in other CNS degenerative and psychiatric
disorders. Following on from the success of two previous
publications in the cholinergic field - Cholinesterases and Their
Inhibitors and Butyrylcholinesterase: Its Function and Inhibitors -
Doctor Ezio Giacobini and Professor Giancarlo Pepeu have prepared
this comprehensive and timely volume, which will be useful to both
clinical and pre-clinical specialists including neurologists,
psychiatrists, neuropsychologists, neuropharmacologists and
neurophysiologists, molecular neurobiologists and neurobiologists
in general.
One of the most impressive advances in the field of neuroscience
over the last decade has been the accumulation of data on
plasticity and regeneration in the nervous system of mammals. The
book represents the contribution of a qroup of neuroscientists to
this rapidly expanding field, through a Conference organized by the
Institute of Developmental Neuroscience and Aging (IDNA). The
meeting was held in Torino, Italy during April 1990 in honor of a
great pioneer in the field of Neuroembryology, Professor Guido
Filogamo. His introduction of the concept of neuroplasticity has
had a significant impact on the study of neurobiology. This volume
is divided into six sections, each focusing on one of the subject
areas covered during the meeting Molecular and Cellular Aspects of
Central and Peripheral Nervous System Development; Hormones,*
Growth Factors, Heurotransmi tters, Xenobiotics and Development; In
Vivo and in Vitro models of Development; Development and Regulation
of Glia; Regeneration; and Aging.
Since the apoE4 allele is a risk factor or susceptibility gene in
late-onset familial and sporadic AD, the mechanism of disease
expression may involve metabolic effects that are isoform specific.
Isoform-specific interactions of apoE therefore become critical in
the mechanism of AD pathogenesis. Detailed characterization of the
binding of the apoE isoforms with proteins and peptides relevant to
the pathology of the disease may be critical in understanding
disease pathogenesis. These critical isoform-specific interactions
of apoE may involve interactions with proteins and pep tides in the
defining neuropathologic lesions of the disease, the
neurofibrillary tangle and senile plaque. Other possible critical
isoform-specific interactions include the mechanism of
internalization, intracellular trafficking, and subsequent
metabolism. In addition, differential post-translational
modifications of apoE isoforms may determine differences in
metabolism contributing to the pathogenesis of the disease.
Oxidation of apoE may confer several isoform-specific,
biochemically distinct properties. Since {3A peptide binds apoE in
the lipoprotein binding domain of the protein and not in the
receptor-binding domain, apoE could target bound {3A4 peptide to
neurons via the LRP receptor. Internalization of the apoEI {3A
peptide complex into the cell, by the same route as the
apoE-containing lipoproteins, would result in incorporation into
primary lysosomes and pH dependent dissociation. The demonstration
of apoE in the cytoplasm of neurons, with isoform-specific
interactions of apoE with the microtubule-binding protein tau
demonstrated in vitro, suggest additional, testable hypotheses of
disease pathogenesis.
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