Animal Models for PD and ALS

Abstract

Current research into neurodegenerative disorders relies heavily on animal models that recapitulate human disease. This chapter focuses on genetic and toxin-based animal models of Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). Early models failed to duplicate many of the hallmarks of these diseases, such as the loss of dopaminergic neurons in PD and motor neuron loss in ALS, and were often dismissed as newer models were developed. Nevertheless, even current models may not fully mimic all facets of disease etiology, progression, or pathology, necessitating continued research into developing models that more closely replicate the clinical manifestations of the disease. For both PD and ALS, genetic models have been generated based on the clinical reports of familial forms of the disease. For PD, models have been created using genes coding for α-synuclein, parkin, LRRK2, DJ-1, and PINK1, while mutations in genes coding for SOD1, FUS/TLS, and TDP-43 have been used for ALS models. For either disease, fewer than 10 % of all cases are linked to genetic causes, whereas the majority of cases are termed sporadic and are likely caused by environmental factors or a combination of environmental factors and genetically imposed susceptibilities. Therefore, a large number of animal models are toxin-based, utilizing chemicals or metals that have been correlated with human disease. As a whole, current animal models serve as adequate substitutes to their human counterparts, providing valuable tools for translational and basic science research in PD and ALS, with the caveat that most models typically do not recapitulate the totality of the human disease. Therefore, this chapter intends to describe the more commonly used animal models for these diseases and relate their limitations.