Table 5.
Phenotypes of human stem cell models of ALS.
| Clinical ALS phenotypes | Human stem cell models of ALS | |||
|---|---|---|---|---|
| SOD1 | FUS | TDP-43 | C9ORF72 | |
| Macroscopic hallmarks | + | + | ± | + |
| Degeneration of upper and lower MNs | + | + | ± | + |
| Vesicle traffic defects | ND | ND | ND | ND |
| Enlarged endosomes vacuolization | + | ND | ND | ND |
| Impaired axonal transport | ND | ND | ND | ND |
| Protein mis-sorting | + | ND | ND | + |
| Ubiquitin-positive protein aggregates | + | + | + | + |
| TDP-43-positive protein aggregates | ND | ND | + | + |
| Neurofilament aggregations (perinuclear) | + | ND | + | + |
| Mitochondrial alteration | + | ND | ND | + |
| Cortical hyperexcitability/excitotoxicity | ND | + | ND | ND |
| Astrogliosis | ND | ND | + | + |
| Microgliosis | ND | ND | ND | ND |
| NMJ and muscle atrophy | Neurite and | ND | Neurite and | Neurite and |
| axonal degeneration | ND | axonal degeneration | axonal degeneration | |
| Hyperexcitability, reduced GABAergic inhibition | + | + | + | + |
Cellular and molecular features presenting in clinical ALS are listed in the far left column. Some of the most frequently found mutations found associated with fALS and sALS are represented at the top and the phenotypes found in iPSCs summarized for each category. +, phenotype; −, no phenotype; ±, variable phenotype; ND, Not determined (yet).