The Use of Stem Cells to Model Amyotrophic Lateral Sclerosis and Frontotemporal Dementia: From Basic Research to Regenerative Medicine

Figure 1

Overview representation of disease pathogenesis of ALS and FTD in cells derived from patient somatic lines. Neurons/motor neurons were differentiated from human induced pluripotent stem cells and varied phenotypes were observed: mutant protein may be mislocalized into a different cellular compartment (TDP-43 [17, 18]); overexpression and downregulation of mutant proteins were observed [18–20]; formation of cellular aggregates [21]; formation of repeat-associated non-ATG (RAN) peptides [22, 23]; formation of RNA foci [22–24]; glutamate toxicity [23]; mitochondria defects [20]; nuclear import/export impairment [25, 26]; formation of neurofilament inclusions [27] and axonal transport defects [20]. In the absence of glia, SOD1 models formed neurofilament inclusions which lead to neurite degeneration in motor neurons [27].