Abstract
Aged dogs are considered the most suitable spontaneous animal model for studying normal aging and neurodegenerative diseases. Elderly canines naturally develop cognitive dysfunction and neuropathological hallmarks similar to those seen in humans, especially Alzheimer's disease-like pathology. Pet dogs also share similar living conditions and diets to humans. Oxidative damage accumulates in the canine brain during aging, making dogs a valid model for translational antioxidant treatment/prevention studies. Evidence suggests the presence of detective protein quality control systems, involving ubiquitin-proteasome system (UPS) and Heat Shock Proteins (HSPs), in the aged canine brain. Further studies on the canine model are needed to clarify the role of age-related changes in UPS activity and HSP expression in neurodegeneration in order to design novel treatment strategies, such as HSP-based therapies, aimed at improving chaperone defences against proteotoxic stress affecting brain during aging.
Highlights
The aged dogs naturally develop cognitive dysfunction and neuropathological hallmarks similar to those seen in normal elderly humans or in patients suffering from neurodegenerative conditions, Alzheimer’s disease (AD)
The aged canines naturally develop cognitive dysfunction and neuropathological hallmarks similar to those seen in humans, especially AD-like pathology
Even though a Heat Shock Proteins (HSPs)-based therapy appears to be a promising strategy for the treatment of diseases characterized by oxidative damage, there are still some major problems that must be overcome before this approach can be successfully applied
Summary
The aged dogs naturally develop cognitive dysfunction and neuropathological hallmarks similar to those seen in normal elderly humans or in patients suffering from neurodegenerative conditions, Alzheimer’s disease (AD). Misfolded proteins with a KFERQ-related motif can be guided by HSPs (the heat shock cognate 70: Hsc or Hsp73) into the lysosome via translocation through the lysosomal-associated membrane transporter (LAMP2A), a process known as chaperone-mediated autophagy (CMA) [59, 65,66,67] During aging, these systems may exhibit a reduced effectiveness and may be overwhelmed by the proteotoxic stress [59, 68, 69] (Figure 1). Altered (increased or reduced) expression of many HSPs has been observed in the brain tissue of aged humans and animals as well as in tissues from elderly patients with neurodegeneration, indicating their involvement in the pathophysiology of aging and neurodegenerative disorders [59, 68] and making them potential targets for therapeutic interventions in aging and aging-related diseases [72, 73]
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