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Fig. 2 | Molecular Neurodegeneration

Fig. 2

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

Fig. 2

Spastin executes microtubule loss after invasion of dendrites by Tau and TTLL6. a Experimental evidence for spastin mediated microtubule breakdown in a neuronal cell model of AD. Spastin was silenced using shRNA with a vector co-expressing mRFP in primary hippocampal neurons aged 16 days in vitro. Cells were then treated with 1 μM Aβ for 3 h. Silencing of spastin results in stable microtubules after Aβ treatment. Cells expressing shRNA show no microtubule reduction in dendrites (arrows, a1). Neighboring untransfected cells with normal spastin levels show loss of microtubules in dendrites after Aβ treatment (a2, arrowheads). b, c Diagrams of proposed mechanisms for microtubule breakdown in AD and overstable microtubules in HSP. (b) In Alzheimer disease and other tauopathies, spastin mediates microtubule disassembly in dendrites in the presence of missorted Tau. (c) In the case of HSP caused by mutations of sp4/SPAST, spastin is unable to sever microtubules, but might still be able to bind them, resulting in overstable and bundled microtubules. Modified from [32, 78]

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