Linked Life Data

20060898

Source:http://linkedlifedata.com/resource/pubmed/id/20060898

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-2-22
pubmed:abstractText
Diverse age-associated neurodegenerative disorders are featured at a molecular level by depositions of self-aggregating molecules, as represented by amyloid beta peptides (Abeta) and tau proteins in Alzheimer's disease, and cascade-type chain reactions are supposedly commenced with biochemical aberrancies of these amyloidogenic components. Mutagenesis and multiplication of the genes encoding Abeta, tau and other pathogenic initiators may accelerate the incipient process at the cascade top, rationalizing generations of transgenic and knock-in animal models of these illnesses. Meanwhile, these genetic manipulations do not necessarily compress the timelines of crucial intermediate events linking amyloidogenesis and neuronal lethality, resulting in an incomplete recapitulation of the diseases. Requirements for modeling the entire cascade can be illustrated by a side-by-side comparison of humans and animal models with the aid of imaging-based biomarkers commonly applicable to different species. Notably, key components in a highly reactive state are assayable by probe-assisted neuroimaging techniques exemplified by positron emission tomography (PET), providing critical information on the in-vivo accessibility of these target molecules. In fact, multispecies PET studies in conjunction with biochemical, electrophysiological and neuropathological tests have revealed putative neurotoxic subspecies of Abeta assemblies, translocator proteins accumulating in aggressive but not neuroprotective microglia, and functionally active neuroreceptors available to endogenous neurotransmitters and exogenous agonistic ligands. Bidirectional translational studies between human cases and model strains based on this experimental paradigm are presently aimed at clarifying the tau pathogenesis, and would be expanded to analyses of disrupted calcium homeostasis and mitochondrial impairments. Since reciprocal causalities among the key processes have indicated an architectural interchangeability between cascade and network connections as an etiological representation, longitudinal imaging assays with manifold probes covering the cascade from top to bottom virtually delineate the network dynamics continuously altering in the course of the disease and its treatment, and therefore expedite the evaluation and optimization of therapeutic strategies intended for suppressing the neurodegenerative pathway over its full length.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-3002
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Print
pubmed:volume
1802
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
373-88
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
In-vivo visualization of key molecular processes involved in Alzheimer's disease pathogenesis: Insights from neuroimaging research in humans and rodent models.
pubmed:affiliation
Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba, Chiba 263-8555, Japan. mhiguchi@nirs.go.jp
pubmed:publicationType
Journal Article, Review