Natural animal models of neurodegenerative protein misfolding diseases

Abstract

Neurodegenerative diseases (NDs) are some of the most debilitating human illnesses. Research over the past 10 years has provided 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 diseases. Importantly, some NDs are not exclusive to human beings, such as transmissible spongiform encephalopathies. Moreover, other diseases which are associated to aging (e.g. Alzheimer's 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 unquestionable, the information obtained from natural non-transgenic models could be very valuable to fully understand the pathogenesis of these devastating diseases.