# name
Modulation of Signal Transduction Pathways in Senescence-Accelerated Mice P8 Strain: A Useful Tool for Alzheimer’s Disease Research

# metadata.dc.description.abstract[].value
Senescence-accelerated mouse (SAM) lines serve as models of aging and age-associated
diseases. The SAMP8 strain has a shortened life span and early-onset manifestations of
senescence with characteristic pathological features observed in elderly humans, including
deficits in learning and memory. In brains of SAMP8 mice, the processing of amyloid
precursor protein (APP) is altered, resulting in excess production and accumulation of
amyloid-􀇃 peptide (A􀇃), tau is hyper-phosphorylated, and oxidative stress is increased.
These phenotypic abnormalities are quite reminiscent of the findings in human brains with
Alzheimer’s disease (AD). Mechanistically, metabolic pathways that are responsible for the
generation of reactive oxygen species (ROS) are increased, while antioxidant systems are
reduced in activity in the cerebral cortex of aged SAMP8 mice. Besides these structural and
metabolic alterations, brains of aged SAMP8 mice exhibit neurochemical abnormalities such
as altered signaling through G protein-coupled receptors for 5-hydroxytryptamine,
acetylcholine, adenosine, dopamine, melatonin, glutamate and GABA, ion channel
receptors, and nuclear hormone receptors (e.g. for all-trans-retinoic acid, cortisol or
estradiol). Consequences include alterations in the levels of neurotransmitters, receptor
numbers, receptor binding affinity, and second messengers. Of note is that in AD, G proteincoupled
receptors and/or their corresponding signaling pathways are often impaired.
Together, the observations in aged SAMP8 mouse brains provide convincing evidence that this model serves as an excellent research tool for studying AD pathogenesis and strategies
for treatment. Additionally, many of the pathological and neurochemical abnormalities in
SAMP8 mice are linked to altered expression of genes that are integrally related to processes
such as neuroprotection, signal transduction, protein folding/degradation, intracellular
transport and immune response. Several studies have already utilized pharmacological or
dietary measures to restore cognitive function and enhance neuroprotection in aged SAMP8
mice, suggesting that these approaches may have applications in the treatment of AD. This
review compiles available data concerning the signaling pathways that are altered in
SAMP8 mice, and compares the effects to known abnormalities in AD brains.

# metadata.dc.relation.ispartof[].value
Chapter 15 in: De La Monte, Suzanne. 2011. The Clinical Spectrum of Alzheimer's Disease: The Charge Toward Comprehensive Diagnostic and Therapeutic Strategies. IntechOpen. ISBN: 978-953-51-6785-3. DOI: 10.5772/722. pp: 297-330.

# metadata.dc.rights[].value
cc by-nc-sa (c) Albasanz, José Luis et al., 20xx

# metadata.dc.source[].value
Llibres / Capítols de llibre (Patologia i Terapèutica Experimental)

# metadata.dc.title[].value
Modulation of Signal Transduction Pathways in Senescence-Accelerated Mice P8 Strain: A Useful Tool for Alzheimer’s Disease Research