Research Paper Volume 13, Issue 20 pp 23620—23636
Nmnat2 attenuates amyloidogenesis and up-regulates ADAM10 in AMPK activity-dependent manner
- 1 Department of Neurology, Translational Medicine Center, Huaihe Hospital Affiliated to Henan University, Kaifeng 475000, Henan, China
- 2 Department of Pathophysiology, Key Laboratory of Neurological Disease of National Education Ministry and Hubei Province, Institute for Brain Research, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
- 3 Department of Respiratory, Huaihe Hospital Affiliated to Henan University, Kaifeng 475000, Henan, China
- 4 Brain Research Laboratory, Henan University, Kaifeng 475004, Henan, China
- 5 Department of Physiology, Basic Medical College, Zhengzhou University, Zhengzhou 450001, Henan, China
- 6 Department of Microbiology, Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng 475004, Henan, China
- 7 Department of Psychiatry, Henan Key Lab of Biological Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang 453002, Henan, China
Received: October 14, 2020 Accepted: October 3, 2021 Published: October 13, 2021https://doi.org/10.18632/aging.203634
How to Cite
Copyright: © 2021 Cheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Amyloid-β (Aβ) accumulating is considered as a causative factor for formation of senile plaque in Alzheimer’s disease (AD), but its mechanism is still elusive. The Nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2), a key redox cofactor for energy metabolism, is reduced in AD. Accumulative evidence has shown that the decrease of α-secretase activity, a disintegrin and metalloprotease domain 10 (ADAM10), is responsible for the increase of Aβ productions in AD patient’s brain. Here, we observe that the activity of α-secretase ADAM10 and levels of Nmnat2 are significantly decreased, meanwhile there is a simultaneous elevation of Aβ in Tg2576 mice. Over-expression of Nmnat2 increases the mRNA expression of α-secretase ADAM10 and its activity and inhibits Aβ production in N2a/APPswe cells, which can be abolished by Compound C, an AMPK antagonist, suggesting that AMPK is involved in over-expression of Nmnat2 against Aβ production. The further assays demonstrate that Nmnat2 activates AMPK by up-regulating the ratio of NAD+/NADH, moreover AMPK agonist AICAR can also increase ADAM10 activity and reduces Aβ1-40/1-42. Taken together, Nmnat2 suppresses Aβ production and up-regulates ADAM10 in AMPK activity-dependent manner, suggesting that Nmnat2 may serve as a new potential target in arresting AD.