Vegetable Oil-derived ‘ Hydroxynonenal ’ Causes Diverse Cell Death Possibly Leading to Alzheimer ’s and Related Lifestyle Diseases
*Corresponding Author: Tetsumori Yamashima, Departments of Psychiatry and Behavioural Science, Kanazawa University Graduate School of Medical Science, Japan, Tel: +81(90)2129-1429, Fax: +81(76)247-1338, Email: yamashima215@gmail.comReceived Date: Oct 26, 2019 / Accepted Date: Jan 01, 2020 / Published Date: Jan 08, 2020
Citation: Yamashima T, Boontem P, Shimizu H, Ota T, Kikuchi M, et al. (2020) Vegetable Oil-derived ‘Hydroxynonenal’ Causes Diverse Cell Death Possibly Leading to Alzheimer’s and Related Lifestyle Diseases. J Alzheimers Dis Parkinsonism 10: 483.
Copyright: © 2020 Yamashima T, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Abstract
Objective: The real culprit of Alzheimer’s disease remains unelucidated for more than a century. Since Alzheimer’s disease is often associated with lifestyle diseases such as type 2 diabetes, there should be a common causative factor. To elucidate this, we focused on ‘Hydroxynonenal’ that is generated during deep frying of ω-6 Polyunsaturated Fatty Acids (PUFAs).
Methods: Monkeys after consecutive injections of the synthetic Hydroxynonenal were histologically studied to determine, whether it can induce cell degeneration/death in the brain, liver and pancreas.
Results: In all of the five monkeys injected, hippocampal neurons, hepatocytes and β cells after Hydroxynonenal injections revealed similar microcystic degeneration and scattered cell death by light microscopy. By electron microscopy, degenerating cells generally showed lysosomal permeabilization or rupture, electron-luscent cytoplasm, nuclear dissolution, membrane disruption, mitochondrial injury and accumulation of autophagosomes containing cell debris. The number of vivid lysosomes were remarkably decreased, compared to the controls.
Conclusion: Targeting ‘Hydroxynonenal’ would help elucidate the pathogenesis of not only Alzheimer’s disease but also related lifestyle diseases. Since ω-6 PUFAs can induce both GPR40 activation leading to calpain activation and intrinsic Hydroxynonenal generation leading to Hsp70.1 carbonylation, calpain-mediated cleavage of carbonylated Hsp70.1 was thought to disturb lysosomal membrane integrity to induce programmed cell death.