Table 1.
Effects on microtubules in AD, AD models, models of tauopathy and SPAST-HSP models
| Disease model | Effects on microtubules | Suggested cause | Therapeutic/mechanistic intervention | Reference |
|---|---|---|---|---|
| AD patient study | microtubule reduction | - | - | [10] |
| AD model: Primary neurons exposed to oligomeric Aβ |
specific loss of dendritic microtubules | spastin/TTLL6 mediated aberrant severing caused by Tau missorting and phosphorylation | Taxol, MARK2 overexpression, spastin suppression | [78, 80, 81] |
| AD model: Primary neurons exposed to prefibrillar Aβ | loss of microtubules | N-terminal domain of Tau (aa 1–248) | - | [37] |
| Tauopathy model: tg-mice with 0N3R Tau with a pathological mutation (P301L) | decreased microtubule stability | - | Epothilone D | [82] |
| Model of HSP: tg-mice (putative KO) and derived primary neurons | decreased number of dynamic microtubules; progressive axonopathy | axonal swellings | Nocodazole, Taxol, Vinblastine | [19, 70] |
| Model of HSP: patient derived olfactory neurons | low levels of acetylated tubulin, slow peroxisome trafficking | - | taxol, vinblastine, epothilone, noscapine | [18] |
| Model of HSP: Overexpression of mutated spastin | decreased microtubule dynamics | binding of severing deficient spastin isoform M1 to microtubules | reduction of M1 isoform; M85 isoform had no effect | [62, 63] |
| Model of HSP: iPSC with SPAST mutations | neurite swellings with disrupted microtubules | - | Overexpression of spastin isoforms M1 and M87 | [26] |
| Model of HSP: iPSC cells and knockdown hESCs | increased levels of acetylated tubulin | - | vinblastine | [14] |
| Model of HSP: tg-mice (putative KO) | - | axonal swellings, perturbed transport | - | [36] |
| Model of HSP: zebrafish KD of spastin | impaired MT dynamics | spastin function required for physiological MT dynamics | no beneficial effect of nocodazole | [9] |
| Drosophila model of axon regeneration after axotomy in heterozygous KO and spastin overexpression | no effect on microtubule polarity or developmental neuritic outgrowth | heterozygous KO of spastin impairs axonal regeneration | overexpression of spastin also results in impaired axonal regeneration | [66] |