Abstract:
:One major pathological process in Alzheimer's disease is mediated by hyperphosphorylated tau, which includes altered microtubules (MTs) and functions associated with tau. A potential way to compensate for altered MT function is to use an MT stabilizer, such as epothilone D (EpoD). Previous studies have demonstrated improved cognitive functions and axonal transport by EpoD in tau-mutation mice. Here, we demonstrated that extended EpoD treatment also has beneficial effects on APP/PS1 double-transgenic mice, improving their motor and spatial memory, increasing key synaptic protein levels, while not affecting amyloid plaque density or level of tau phosphorylation. Interestingly, EpoD appears to improve the retrieval of formed memories. We also observed improved axonal transport of mitochondria in cultured neurons from APP/PS1 mice. In addition, higher level of perineuronal nets are found in APP/PS1 mice injected with EpoD, suggesting potential contributions of increased inhibition. Our results suggest potential therapeutic value of EpoD in treating Alzheimer's disease.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Guo B,Huang Y,Gao Q,Zhou Qdoi
10.1016/j.neurobiolaging.2020.09.011subject
Has Abstractpub_date
2020-12-01 00:00:00pages
223-232eissn
0197-4580issn
1558-1497pii
S0197-4580(20)30288-8journal_volume
96pub_type
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