Alzheimer's disease models and functional genomics-how many needles are there in the haystack?

Goetz, Juergen, Matamales, Miriam, Goetz, Naeman N., Ittner, Lars M. and Eckert, Anne (2012) Alzheimer's disease models and functional genomics-how many needles are there in the haystack?. Frontiers in Physiology, 3 320: 320.1-320.14.


Author Goetz, Juergen
Matamales, Miriam
Goetz, Naeman N.
Ittner, Lars M.
Eckert, Anne
Title Alzheimer's disease models and functional genomics-how many needles are there in the haystack?
Journal name Frontiers in Physiology   Check publisher's open access policy
Publication date 2012-08-08
Sub-type Article
DOI 10.3389/fphys.2012.00320
Volume number 3
Issue number 320
ISSN 1664-042X
Start page 320.1
End page 320.14
Total pages 14
Place of publication Lausanne, Switzerland
Publisher Frontiers Research Foundation
Collection year 2013
Language eng
Abstract Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) are complex human brain disorders that affect an increasing number of people worldwide. With the identification first of the proteins that aggregate in AD and FTLD brains and subsequently of pathogenic gene mutations that cause their formation in the familial cases, the foundation was laid for the generation of animal models. These recapitulate essential aspects of the human conditions; expression of mutant forms of the amyloid-β protein-encoding APP gene in mice reproduces amyloid-β (Aβ) plaque formation in AD, while that of mutant forms of the tau-encoding microtubule-associated protein tau (MAPT) gene reproduces tau-containing neurofibrillary tangle formation, a lesion that is also prevalent in FTLD-Tau. The mouse models have been complemented by those in lower species such as C. elegans or Drosophila, highlighting the crucial role for Aβ and tau in human neurodegenerative disease. In this review, we will introduce selected AD/FTLD models and discuss how they were instrumental, by identifying deregulated mRNAs, miRNAs and proteins, in dissecting pathogenic mechanisms in neurodegenerative disease. We will discuss some recent examples, which includes miRNA species that are specifically deregulated by Aβ, mitochondrial proteins that are targets of both Aβ and tau, and the nuclear splicing factor SFPQ that accumulates in the cytoplasm in a tau-dependent manner. These examples illustrate how a functional genomics approach followed by a careful validation in experimental models and human tissue leads to a deeper understanding of the pathogenesis of AD and FTLD and ultimately, may help in finding a cure.
Keyword Alzheimer's disease
Amyloid
Frontotemporal dementia
Kinase
Phosphatase
Proteomic
Tau
Transcriptomic
Q-Index Code CX
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article #320

Document type: Journal Article
Sub-type: Article
Collection: Queensland Brain Institute Publications
 
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Created: Wed, 07 Nov 2012, 14:12:31 EST by Debra McMurtrie on behalf of Queensland Brain Institute