Natural Animal Models of Neurodegenerative Protein Misfolding Diseases

Ines      Moreno-Gonzalez; Claudio      Soto

Abstract

Neurodegenerative diseases (NDs) are some of the most debilitating human illnesses. Research over the past 10 years has pro-vided evidence for a common mechanism of neurodegeneration in which the critical event is the brain accumulation of misfolded protein aggregates. Although it is well established that misfolded proteins play an important role in these diseases, the mechanisms by which they cause cellular and tissue dysfunction are still unknown. To understand the molecular basis of NDs and to develop therapeutic strategies against them, numerous transgenic rodent models have been produced, which reproduce some (but not all) of the features of these dis-eases. Importantly, some NDs are not exclusive to human beings, such as transmissible spongiform encephalopathies. Moreover, other diseases which are associated to aging (e.g. Alzheimers disease) could be studied in aged mammals, which could reproduce the human disease in a more natural way. Although the usefulness of transgenic mice is unquestio nable, the information obtained from natural non-transgenic models could be very valuable to fully understand the pathogenesis of these devastating diseases.

Keywords: Prion, protein misfolding, natural model, non-transgenic, Alzheimer's disease, amyloid, Neurodegenerative diseases (NDs), aging, transgenic mice, transmissible spongiform encephalopathies