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Advanced Neurology Early inhibition of PDK1 prevents AD-like pathology

Since ribosomal kinase S6 is a key member of the Ethics approval and consent to participate
mTOR signaling pathway [15,16,21] , the decreased pS6 levels
suggest that the activity of mTOR may be reduced in the An animal protocol (AP) for this study was approved by the
Institutional Animal Care and Use Committee (IACUC) of
Pdk1 cKO/5×FAD cortex. Since previous evidence has the MARC at Nanjing University.
shown that S6 is essential for ribosome biogenesis [61] ,
it is likely that ribosome biogenesis may be regulated Consent for publication
by PDK1 via S6 [37] . In essence, the following molecular
and cellular mechanisms may be responsible for the Not applicable.
prevention effects on AD-like pathology as observed in Availability of data
Pdk1 cKO/5×FAD mice. First, PDK1 deletion causes a
reduction in mTOR signaling and subsequently inhibits The experimental materials used in this study are available
the activity of S6. Second, the deactivation of S6 may from corresponding authors on reasonable request.
impair ribosome-dependent protein synthesis, which References
then downregulates APP expression at the translational
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Acknowledgments 5. Hardy, J, Selkoe DJ, 2002, The amyloid hypothesis of
We thank Xiaochuan Zou for technical assistance. Alzheimer’s disease: Progress and problems on the road to
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Funding 6. Goedert M, Eisenberg DS, Crowther RA, 2017, Propagation
of Tau aggregates and neurodegeneration. Ann Rev Neurosci,
This study was partially supported by the National Natural 40: 189–210.
Science Foundation of China (NSFC91849113), the
Natural Key Research and Development Program of China 7. Mintun MA, Lo AC, Evans CD, et al., 2021, Donanemab in
early Alzheimer’s disease. N Engl J Med, 384: 1691–1704.
(2022ZD0211803), the Natural Science Foundation of
Jiangsu (BK20201255), and the Changzhou Municipal Key 8. Sevigny J, Chiao P, Bussiere T, et al., 2016, The antibody
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Conflict of interest 9. Peng Y, Hu Y, Xu S, et al., 2012, L-3-n-butylphthalide
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The authors have no conflicts of interest to declare.
in AbetaPP/PS1-Alzheimer’s transgenic mice. J Alzheimers
Author contributions Dis, 29: 379–391.
10. Peng Y, Sun J, Hon S, et al., 2010, L-3-n-butylphthalide
Conceptualization: Yimin Hu, Bing Zhang, and Guiquan improves cognitive impairment and reduces amyloid-beta
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Formal analysis: Xiaolian Ye, Liyang Yao, Wenhao Chen, 30: 8180–8189.
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Volume 1 Issue 3 (2022) 10 https://doi.org/10.36922/an.v1i3.153