New insights on the mechanisms of disease course variability in ALS from mutant SOD1 mouse models.

Nardo Giovanni, Trolese Maria Chiara, Tortarolo Massimo, Vallarola Aantonio, Freschi Mattia, Pasetto Laura, Bonetto Valentina, Bendotti Caterina,

Brain pathology (Zurich, Switzerland), January 18, 2016

Amyotrophic Lateral Sclerosis (ALS) is a heterogeneous disease in terms of progression rate and survival. This is probably one of the reasons for the failure of many clinical trials and the lack of effective therapies. A similar variability is also found in SOD1(G93A) mouse models based on their genetic background. For example, when the SOD1(G93A) transgene is expressed in C57BL6 background the phenotype is mild with consistently slower disease progression if compared to the 129Sv mice expressing the same amount of transgene but displaying a faster progression and shorter lifespan. In this review we summarize and discuss data obtained from the analysis of these two mouse models under different aspects such as the motor phenotype, the neuropathological alterations in the central nervous system (CNS) and peripheral nervous system (PNS), the motor neuron autonomous and non-cell autonomous mechanisms in attempt to provide key elements to understand the causes of the different rates of disease progression. In addition, we report relevant findings on the identification of promising prognostic biomarkers by the comparative analysis of the two ALS mouse models. We believe that this analysis can hint at new strategies for effective therapeutic intervention in ALS aimed to slow down significantly or even block the course of disease. This article is protected by copyright. All rights reserved.

© 2016 International Society of Neuropathology.

Pubmed Link: 26780365

DOI: 10.1111/bpa.12351