In:
Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2022 ( 2022-8-27), p. 1-15
Abstract:
Alzheimer’s disease (AD) is a progressive and irreversible neurodegenerative disorder for which there is no effective therapeutic strategy. PcActx peptide from the transcriptome of zoantharian Palythoa caribaeorum has recently been identified and verified as a novel antagonist of transient receptor potential cation channel subfamily V member 1 (TRPV1). In the present study, we further investigated the neuroprotective potential of PcActx peptide and its underlying mechanism of action, in an N2a/APP cell model of AD. Both Western blot and RT-PCR analysis revealed that PcActx peptide markedly inhibited the production of amyloid-related proteins and the expression of BACE1, PSEN1, and PSEN2. Moreover, PcActx peptide notably attenuated the capsaicin-stimulated calcium response and prevented the phosphorylation of CaMKII and CaMKIV (calcium-mediated proteins) in N2a/APP cells. Further investigation indicated that PcActx peptide significantly suppressed ROS generation through Nrf2 activation, followed by enhanced NQO1 and HO-1 levels. In addition, PcActx peptide remarkably improved Akt phosphorylation at Ser 473 (active) and Gsk3β phosphorylation at Ser 9 (inactive), while pharmacological inhibition of the Akt/Gsk3β pathway significantly attenuated PcActx-induced Nrf2 activation and amyloid downregulation. In conclusion, PcActx peptide functions as a TRPV1 modulator of intercellular calcium homeostasis, prevents AD-like amyloid neuropathology via Akt/Gsk3β-mediated Nrf2 activation, and shows promise as an alternative therapeutic agent for AD.
Type of Medium:
Online Resource
ISSN:
1942-0994
,
1942-0900
DOI:
10.1155/2022/1544244
Language:
English
Publisher:
Hindawi Limited
Publication Date:
2022
detail.hit.zdb_id:
2455981-7
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