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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]