Orietta Pansarasa

By Diamanti Luca, Zucchi Elisabetta, Pansarasa Orietta, Ceroni Mauro and Cereda Crisitna

In 1993, the first superoxide dismutase 1 (SOD1) mutation in amyotrophic lateral sclerosis (ALS) patients has been described by Rosen et al. successively, the scientific literature focused on the role of SOD1 in the pathogenesis of ALS. While a clear genetic scenario has been presented, heterogeneous data have been formulated regarding transcriptional and post-transcriptional regulation of SOD1 so far. In particular, the dilemma concerns the SOD1 protein expression, in the direction of a loss of function of the wild-type SOD1 or a toxic gain of function of the altered SOD1, both in FALS (mutant-SOD1) and in SALS (misfolded-SOD1). In this chapter, we focus on the evolution of scientific knowledge about SOD1 protein in ALS patients, reviewing in detail the results obtained using peripheral blood cells in this research field. To conclude, we propose a brief summary of the described clinical correlation and discuss the possible SOD1 implication as a biomarker of ALS.

Part of the book: Update on Amyotrophic Lateral Sclerosis

By Matteo Bordoni, Valentina Fantini, Orietta Pansarasa and Cristina Cereda

In the last decade, the finding that somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) leads to a great improvement of research involving the use of differentiated stem cells as model of diseases. In the field of neurodegeneration, iPSC technology allowed to culture in vitro all the types of patient-specific neurons, not only helping the discovery of diseases’ etiopathology but also testing new drugs with a personalized medicine approach. Moreover, iPSCs can be combined with the 3D bioprinting technology, allowing physiological cell-to-cell interactions, given by a combination of several biomaterials, scaffolds, and cells. This technology combines bioplotter and biomaterials which can encapsulate several types of cells, e.g., iPSCs or differentiated neurons, to develop an innovative cellular model. iPSCs and 3D cell cultures’ technologies represent the first step to obtain a more reliable model, like an organoid to facilitate neurodegenerative diseases’ investigation.

Part of the book: Recent Advances in Neurodegeneration

By Orietta Pansarasa, Stella Gagliardi, Daisy Sproviero and Cristina Cereda

Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disorder characterized by the selective death of upper and lowers motor neurons in spinal cord, brain stem, and motor cortex, which leads to paralysis and death within 2–3 years of onset. Deeply sequencing technologies, to simultaneously analyze the transcriptional expression of thousands of genes, offered new possibilities to focus on ALS pathogenesis and, most notably, to find new potential targets for novel treatments. The present book chapter illustrates recent advances in transcriptomic studies in animal models and human samples and in new molecular targets related to ALS pathogenesis and disease progression. Additionally, new insights into the involvement of altered transcriptional profiles of noncoding RNAs (microRNA and lncRNA) and ALS-associated ribosomal binding proteins have been investigated, to understand the functional consequences of extensive RNA dysregulation in ALS. Attention has been also turned on how transcriptome alterations could highlight new molecular targets for drug development.

Part of the book: Amyotrophic Lateral Sclerosis