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Table 1 Effects on microtubules in AD, AD models, models of tauopathy and SPAST-HSP models

From: Tau missorting and spastin-induced microtubule disruption in neurodegeneration: Alzheimer Disease and Hereditary Spastic Paraplegia

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]