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Mitochondrial aldehyde dehydrogenase (ALDH2) rescues cardiac contractile dysfunction in an APP/PS1 murine model of Alzheimer’s disease via inhibition of ACSL4-dependent ferroptosis

Abstract

Alzheimer’s disease (AD) is associated with high incidence of cardiovascular events but the mechanism remains elusive. Our previous study reveals a tight correlation between cardiac dysfunction and low mitochondrial aldehyde dehydrogenase (ALDH2) activity in elderly AD patients. In the present study we investigated the effect of ALDH2 overexpression on cardiac function in APP/PS1 mouse model of AD. Global ALDH2 transgenic mice were crossed with APP/PS1 mutant mice to generate the ALDH2-APP/PS1 mutant mice. Cognitive function, cardiac contractile, and morphological properties were assessed. We showed that APP/PS1 mice displayed significant cognitive deficit in Morris water maze test, myocardial ultrastructural, geometric (cardiac atrophy, interstitial fibrosis) and functional (reduced fractional shortening and cardiomyocyte contraction) anomalies along with oxidative stress, apoptosis, and inflammation in myocardium. ALDH2 transgene significantly attenuated or mitigated these anomalies. We also noted the markedly elevated levels of lipid peroxidation, the essential lipid peroxidation enzyme acyl-CoA synthetase long-chain family member 4 (ACSL4), the transcriptional regulator for ACLS4 special protein 1 (SP1) and ferroptosis, evidenced by elevated NCOA4, decreased GPx4, and SLC7A11 in myocardium of APP/PS1 mutant mice; these effects were nullified by ALDH2 transgene. In cardiomyocytes isolated from WT mice and in H9C2 myoblasts in vitro, application of Aβ (20 μM) decreased cell survival, compromised cardiomyocyte contractile function, and induced lipid peroxidation; ALDH2 transgene or activator Alda-1 rescued Aβ-induced deteriorating effects. ALDH2-induced protection against Aβ-induced lipid peroxidation was mimicked by the SP1 inhibitor tolfenamic acid (TA) or the ACSL4 inhibitor triacsin C (TC), and mitigated by the lipid peroxidation inducer 5-hydroxyeicosatetraenoic acid (5-HETE) or the ferroptosis inducer erastin. These results demonstrate an essential role for ALDH2 in AD-induced cardiac anomalies through regulation of lipid peroxidation and ferroptosis.

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Fig. 1: The effect of age on myocardial ALDH2 expression and activity and the effect of ALDH2 overexpression on cognitive function, body and organ weight, and cardiac morphology in the APP/PS1 mouse model of Alzheimer’s disease.
Fig. 2: Effect of ALDH2 overexpression on echocardiographic properties in the APP/PS1 mouse model of Alzheimer’s disease.
Fig. 3: Effect of ALDH2 overexpression on cardiomyocyte mechanical and intracellular Ca2+ properties in the APP/PS1 mouse model of Alzheimer’s disease.
Fig. 4: Mitochondrial membrane potential, mitochondrial permeability transition pore (mPTP) opening, myocardial ultrastructure, and reactive oxygen species (ROS) production in hearts from the APP/PS1 mouse model of Alzheimer’s disease with or without the ALDH2 transgene.
Fig. 5: Levels of ALDH2, Aβ, and markers of apoptosis and inflammation in the myocardium of the APP/PS1 mouse model of Alzheimer’s disease with or without ALDH2 overexpression.
Fig. 6: Levels of protein carbonyl damage, lipid peroxidation, the lipid peroxidation regulatory signals SP1 and ACSL4, and ferroptosis in myocardium from the APP/PS1 mouse model of Alzheimer’s disease with or without ALDH2 overexpression.
Fig. 7: Effects of Aβ challenge, inhibition of SP1 and ACSL4 or induction of lipid peroxidation and ferroptosis on cardiomyocyte survival and contractile responses in isolated cardiomyocytes from WT and ALDH2 transgenic mice.
Fig. 8: Effect of Aβ challenge, ALDH2 activation, inhibition of SP1 and ACSL4 or induction of lipid peroxidation and ferroptosis on lipid peroxidation in H9C2 myoblasts.

References

  1. 1.

    Jellinger KA. Pathobiological subtypes of Alzheimer disease. Dement Geriatr Cogn Disord. 2020;49:321–33.

    PubMed  Article  PubMed Central  Google Scholar 

  2. 2.

    Robinson M, Lee BY, Hanes FT. Recent progress in Alzheimer’s disease research, part 2: genetics and epidemiology. J Alzheimers Dis. 2018;61:459.

    PubMed  Article  PubMed Central  Google Scholar 

  3. 3.

    Ryan KC, Ashkavand Z, Norman KR. The role of mitochondrial calcium homeostasis in Alzheimer’s and related diseases. Int J Mol Sci. 2020;21:9153.

    CAS  PubMed Central  Article  Google Scholar 

  4. 4.

    Zhang F, Zhong RJ, Cheng C, Li S, Le WD. New therapeutics beyond amyloid-beta and tau for the treatment of Alzheimer’s disease. Acta Pharmacol Sin. 2021. in press. https://doi.org/10.1038/s41401-020-00565-5.

  5. 5.

    Johnson J, Mercado-Ayon E, Mercado-Ayon Y, Dong YN, Halawani S, Ngaba L, et al. Mitochondrial dysfunction in the development and progression of neurodegenerative diseases. Arch Biochem Biophys 2021. https://doi.org/10.1016/j.abb.2020.108698.

  6. 6.

    Troncone L, Luciani M, Coggins M, Wilker EH, Ho CY, Codispoti KE, et al. Abeta amyloid pathology affects the hearts of patients with Alzheimer’s disease: mind the heart. J Am Coll Cardiol. 2016;68:2395–407.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  7. 7.

    Sanna GD, Nusdeo G, Piras MR, Forteleoni A, Murru MR, Saba PS, et al. Cardiac abnormalities in Alzheimer disease: clinical relevance beyond pathophysiological rationale and instrumental findings? JACC Heart Fail. 2019;7:121–8.

    PubMed  Article  PubMed Central  Google Scholar 

  8. 8.

    Tublin JM, Adelstein JM, Del Monte F, Combs CK, Wold LE. Getting to the heart of Alzheimer disease. Circ Res. 2019;124:142–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  9. 9.

    Yang M, Li C, Zhang Y, Ren J. Interrelationship between Alzheimer’s disease and cardiac dysfunction: the brain-heart continuum? Acta Biochim Biophys Sin (Shanghai). 2020;52:1–8.

    CAS  Article  Google Scholar 

  10. 10.

    Zhang B, Bian X, He P, Fu X, Higuchi K, Yang X, et al. The toxicity mechanisms of action of Abeta25-35 in isolated rat cardiac myocytes. Molecules. 2014;19:12242–57.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  11. 11.

    Benenati S, Canale C, De Marzo V, Della Bona R, Rosa G, Porto I. Atrial fibrillation and Alzheimer disease: a conundrum. Eur J Clin Invest. 2021. https://doi.org/10.1111/eci.13451.

  12. 12.

    Omoya R, Miyajima M, Ohta K, Suzuki Y, Aoki A, Fujiwara M, et al. Heart rate response to orthostatic challenge in patients with dementia with Lewy bodies and Alzheimer’s disease. Psychogeriatrics. 2021;21:62–70.

    PubMed  Article  PubMed Central  Google Scholar 

  13. 13.

    Wang S, Wang L, Qin X, Turdi S, Sun D, Culver B, et al. ALDH2 contributes to melatonin-induced protection against APP/PS1 mutation-prompted cardiac anomalies through cGAS-STING-TBK1-mediated regulation of mitophagy. Signal Transduct Target Ther. 2020;5:119.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  14. 14.

    Khan S, Kamal MA. Cardiac biomarkers in stroke, Alzheimer’s disease, and other dementia. Are they of use? A brief overview of data from recent investigations. CNS Neurol Disord Drug Targets. 2021. https://doi.org/10.2174/1871527319666201005171003.

  15. 15.

    Mohmmad Abdul H, Wenk GL, Gramling M, Hauss-Wegrzyniak B, Butterfield DA. APP and PS-1 mutations induce brain oxidative stress independent of dietary cholesterol: implications for Alzheimer’s disease. Neurosci Lett. 2004;368:148–50.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  16. 16.

    Nakajima M, Moriizumi E, Koseki H, Shirasawa T. Presenilin 1 is essential for cardiac morphogenesis. Dev Dyn. 2004;230:795–9.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  17. 17.

    Turdi S, Guo R, Huff AF, Wolf EM, Culver B, Ren J. Cardiomyocyte contractile dysfunction in the APPswe/PS1dE9 mouse model of Alzheimer’s disease. PLoS One. 2009;4:e6033.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  18. 18.

    Taniuchi N, Niidome T, Goto Y, Akaike A, Kihara T, Sugimoto H. Decreased proliferation of hippocampal progenitor cells in APPswe/PS1dE9 transgenic mice. Neuroreport. 2007;18:1801–5.

    PubMed  Article  PubMed Central  Google Scholar 

  19. 19.

    Webster SJ, Bachstetter AD, Nelson PT, Schmitt FA, Van Eldik LJ. Using mice to model Alzheimer’s dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models. Front Genet. 2014;5:88.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  20. 20.

    Chen CH, Sun L, Mochly-Rosen D. Mitochondrial aldehyde dehydrogenase and cardiac diseases. Cardiovasc Res. 2010;88:51–7.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  21. 21.

    Hao PP, Chen YG, Wang JL, Wang XL, Zhang Y. Meta-analysis of aldehyde dehydrogenase 2 gene polymorphism and Alzheimer’s disease in East Asians. Can J Neurol Sci. 2011;38:500–6.

    PubMed  Article  PubMed Central  Google Scholar 

  22. 22.

    Ma L, Lu ZN. Role of ADH1B rs1229984 and ALDH2 rs671 gene polymorphisms in the development of Alzheimer’s disease. Genet Mol Res. 2016;15, https://doi.org/10.4238/gmr.15048740.

  23. 23.

    Chen J, Huang W, Cheng CH, Zhou L, Jiang GB, Hu YY. Association between aldehyde dehydrogenase-2 polymorphisms and risk of Alzheimer’s disease and Parkinson’s disease: a meta-analysis based on 5,315 Individuals. Front Neurol. 2019;10:290.

    PubMed  PubMed Central  Article  Google Scholar 

  24. 24.

    Wang B, Wang J, Zhou S, Tan S, He X, Yang Z, et al. The association of mitochondrial aldehyde dehydrogenase gene (ALDH2) polymorphism with susceptibility to late-onset Alzheimer’s disease in Chinese. J Neurol Sci. 2008;268:172–5.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  25. 25.

    Ohta S. [Roles of mitochondrial dysfunctions in Alzheimer’s disease–contribution of deficiency of ALDH 2]. Rinsho Shinkeigaku. 2000;40:1231–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Komatsu M, Shibata N, Ohnuma T, Kuerban B, Tomson K, Toda A, et al. Polymorphisms in the aldehyde dehydrogenase 2 and dopamine beta hydroxylase genes are not associated with Alzheimer’s disease. J Neural Transm (Vienna). 2014;121:427–32.

    CAS  Article  Google Scholar 

  27. 27.

    Shin IS, Stewart R, Kim JM, Kim SW, Yang SJ, Shin HY, et al. Mitochondrial aldehyde dehydrogenase polymorphism is not associated with incidence of Alzheimer’s disease. Int J Geriatr Psychiatry. 2005;20:1075–80.

    PubMed  Article  PubMed Central  Google Scholar 

  28. 28.

    Zhou S, Huriletemuer, Wang J, Zhang C, Zhao S, Wang de S, et al. Absence of association on aldehyde dehydrogenase 2 (ALDH2) polymorphism with Mongolian Alzheimer patients. Neurosci Lett. 2010;468:312–5.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  29. 29.

    Reichert CO, de Freitas FA, Sampaio-Silva J, Rokita-Rosa L, Barros PL, Levy D, et al. Ferroptosis mechanisms involved in neurodegenerative diseases. Int J Mol Sci. 2020;21:8765.

    CAS  PubMed Central  Article  Google Scholar 

  30. 30.

    Tang D, Chen X, Kang R, Kroemer G. Ferroptosis: molecular mechanisms and health implications. Cell Res. 2021;31:107–25.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  31. 31.

    Stockwell BR, Friedmann Angeli JP, Bayir H, Bush AI, Conrad M, Dixon SJ, et al. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell. 2017;171:273–85.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  32. 32.

    Yin Z, Ding G, Chen X, Qin X, Xu H, Zeng B, et al. Beclin1 haploinsufficiency rescues low ambient temperature-induced cardiac remodeling and contractile dysfunction through inhibition of ferroptosis and mitochondrial injury. Metabolism. 2020;113:154397.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  33. 33.

    Ren J, Zhang Y. Targeting autophagy in aging and aging-related cardiovascular diseases. Trends Pharmacol Sci. 2018;39:1064–76.

    CAS  Google Scholar 

  34. 34.

    Gonciarz RL, Collisson EA, Renslo AR. Ferrous iron-dependent pharmacology. Trends Pharmacol Sci. 2021;42:7–18.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  35. 35.

    Pang J, Peng H, Wang S, Xu X, Xu F, Wang Q, et al. Mitochondrial ALDH2 protects against lipopolysaccharide-induced myocardial contractile dysfunction by suppression of ER stress and autophagy. Biochim Biophys Acta Mol Basis Dis. 2019;1865:1627–41.

    CAS  PubMed  Article  Google Scholar 

  36. 36.

    Wang S, Wang C, Turdi S, Richmond KL, Zhang Y, Ren J. ALDH2 protects against high fat diet-induced obesity cardiomyopathy and defective autophagy: role of CaM kinase II, histone H3K9 methyltransferase SUV39H, Sirt1, and PGC-1alpha deacetylation. Int J Obes (Lond). 2018;42:1073–87.

    CAS  Article  Google Scholar 

  37. 37.

    Turdi S, Han X, Huff AF, Roe ND, Hu N, Gao F, et al. Cardiac-specific overexpression of catalase attenuates lipopolysaccharide-induced myocardial contractile dysfunction: role of autophagy. Free Radic Biol Med. 2012;53:1327–38.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  38. 38.

    Doser TA, Turdi S, Thomas DP, Epstein PN, Li SY, Ren J. Transgenic overexpression of aldehyde dehydrogenase-2 rescues chronic alcohol intake-induced myocardial hypertrophy and contractile dysfunction. Circulation. 2009;119:1941–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  39. 39.

    Zhang B, He P, Lu Y, Bian X, Yang X, Fu X, et al. HSF1 relieves amyloid-beta-induced cardiomyocytes apoptosis. Cell Biochem Biophys. 2015;72:579–87.

    CAS  PubMed  Article  Google Scholar 

  40. 40.

    Sankpal UT, Ingersoll SB, Ahmad S, Holloway RW, Bhat VB, Simecka JW, et al. Association of Sp1 and survivin in epithelial ovarian cancer: Sp1 inhibitor and cisplatin, a novel combination for inhibiting epithelial ovarian cancer cell proliferation. Tumour Biol. 2016;37:14259–69.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  41. 41.

    Yamamoto T, Endo J, Kataoka M, Matsuhashi T, Katsumata Y, Shirakawa K, et al. Palmitate induces cardiomyocyte death via inositol requiring enzyme-1 (IRE1)-mediated signaling independent of X-box binding protein 1 (XBP1). Biochem Biophys Res Commun. 2020;526:122–7.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  42. 42.

    Yuan H, Li X, Zhang X, Kang R, Tang D. Identification of ACSL4 as a biomarker and contributor of ferroptosis. Biochem Biophys Res Commun. 2016;478:1338–43.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  43. 43.

    Nagahora N, Yamada H, Kikuchi S, Hakozaki M, Yano A. Nrf2 activation by 5-lipoxygenase metabolites in human umbilical vascular endothelial cells. Nutrients. 2017;9:1001.

    PubMed Central  Article  CAS  Google Scholar 

  44. 44.

    Turdi S, Hu N, Ren J. Tauroursodeoxycholic acid mitigates high fat diet-induced cardiomyocyte contractile and intracellular Ca2+ anomalies. PLoS One. 2013;8:e63615.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  45. 45.

    Li Q, Wu S, Li SY, Lopez FL, Du M, Kajstura J, et al. Cardiac-specific overexpression of insulin-like growth factor 1 attenuates aging-associated cardiac diastolic contractile dysfunction and protein damage. Am J Physiol Heart Circ Physiol. 2007;292:H1398–403.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  46. 46.

    Peng H, Qin X, Chen S, Ceylan AF, Dong M, Lin Z, et al. Parkin deficiency accentuates chronic alcohol intake-induced tissue injury and autophagy defects in brain, liver and skeletal muscle. Acta Biochim Biophys Sin (Shanghai). 2020;52:665–74.

    CAS  Article  Google Scholar 

  47. 47.

    Privratsky JR, Wold LE, Sowers JR, Quinn MT, Ren J. AT1 blockade prevents glucose-induced cardiac dysfunction in ventricular myocytes: role of the AT1 receptor and NADPH oxidase. Hypertension. 2003;42:206–12.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  48. 48.

    Zhang Y, Xia Z, La Cour KH, Ren J. Activation of Akt rescues endoplasmic reticulum stress-impaired murine cardiac contractile function via glycogen synthase kinase-3beta-mediated suppression of mitochondrial permeation pore opening. Antioxid Redox Signal. 2011;15:2407–24.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  49. 49.

    Ren J, Roughead ZK, Wold LE, Norby FL, Rakoczy S, Mabey RL, et al. Increases in insulin-like growth factor-1 level and peroxidative damage after gestational ethanol exposure in rats. Pharmacol Res. 2003;47:341–7.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  50. 50.

    Li Y, Feng D, Wang Z, Zhao Y, Sun R, Tian D, et al. Ischemia-induced ACSL4 activation contributes to ferroptosis-mediated tissue injury in intestinal ischemia/reperfusion. Cell Death Differ. 2019;26:2284–99.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  51. 51.

    Wu S, Ren J. Benfotiamine alleviates diabetes-induced cerebral oxidative damage independent of advanced glycation end-product, tissue factor and TNF-alpha. Neurosci Lett. 2006;394:158–62.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  52. 52.

    Zhao B, Tumaneng K, Guan KL. The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal. Nat Cell Biol. 2011;13:877–83.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  53. 53.

    Subramanian K, Gianni D, Balla C, Assenza GE, Joshi M, Semigran MJ, et al. Cofilin-2 phosphorylation and sequestration in myocardial aggregates: novel pathogenetic mechanisms for idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 2015;65:1199–214.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  54. 54.

    Zhao Y, Wang B, Zhang J, He D, Zhang Q, Pan C, et al. ALDH2 (Aldehyde Dehydrogenase 2) protects against hypoxia-induced pulmonary hypertension. Arterioscler Thromb Vasc Biol. 2019;39:2303–19.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  55. 55.

    Killion EA, Reeves AR, El Azzouny MA, Yan QW, Surujon D, Griffin JD, et al. A role for long-chain acyl-CoA synthetase-4 (ACSL4) in diet-induced phospholipid remodeling and obesity-associated adipocyte dysfunction. Mol Metab. 2018;9:43–56.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  56. 56.

    Yang K, Ren J, Li X, Wang Z, Xue L, Cui S, et al. Prevention of aortic dissection and aneurysm via an ALDH2-mediated switch in vascular smooth muscle cell phenotype. Eur Heart J. 2020;41:2442–53.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  57. 57.

    Zhang Y, Wang C, Zhou J, Sun A, Hueckstaedt LK, Ge J, et al. Complex inhibition of autophagy by mitochondrial aldehyde dehydrogenase shortens lifespan and exacerbates cardiac aging. Biochim Biophys Acta Mol Basis Dis. 2017;1863:1919–32.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  58. 58.

    Hu N, Ren J, Zhang Y. Mitochondrial aldehyde dehydrogenase obliterates insulin resistance-induced cardiac dysfunction through deacetylation of PGC-1alpha. Oncotarget. 2016;7:76398–414.

    PubMed  PubMed Central  Article  Google Scholar 

  59. 59.

    Ge W, Yuan M, Ceylan AF, Wang X, Ren J. Mitochondrial aldehyde dehydrogenase protects against doxorubicin cardiotoxicity through a transient receptor potential channel vanilloid 1-mediated mechanism. Biochim Biophys Acta. 2016;1862:622–34.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  60. 60.

    Ma H, Guo R, Yu L, Zhang Y, Ren J. Aldehyde dehydrogenase 2 (ALDH2) rescues myocardial ischaemia/reperfusion injury: role of autophagy paradox and toxic aldehyde. Eur Heart J. 2011;32:1025–38.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  61. 61.

    Chen CH, Ferreira JC, Gross ER, Mochly-Rosen D. Targeting aldehyde dehydrogenase 2: new therapeutic opportunities. Physiol Rev. 2014;94:1–34.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  62. 62.

    Xu H, Zhang Y, Ren J. ALDH2 and stroke: a systematic review of the evidence. Adv Exp Med Biol. 2019;1193:195–210.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

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Acknowledgements

The research reported in this publication was supported in part by the National Natural Science Foundation of China (82060351, 82000351) and the Natural Science Foundation of Jiangxi Province (20203BBGL73189).

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ZYZ, YDL, YG, WJ, ET, ST, YFG, SYW, WLZ, and XQ performed the experiments; JR, BC, WG, ZHP, and XQ conceived and designed the study and drafted, edited, and approved the paper.

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Correspondence to Jun Ren or Zhao-hui Pei or Xing Qin.

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Zhu, Zy., Liu, Yd., Gong, Y. et al. Mitochondrial aldehyde dehydrogenase (ALDH2) rescues cardiac contractile dysfunction in an APP/PS1 murine model of Alzheimer’s disease via inhibition of ACSL4-dependent ferroptosis. Acta Pharmacol Sin (2021). https://doi.org/10.1038/s41401-021-00635-2

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Keywords

  • Alzheimer’s disease
  • cardiac function
  • landscape perceptions
  • ALDH2
  • lipid peroxidation
  • ferroptosis
  • Alda-1
  • tolfenamic acid; triacsin C; 5-HETE; erastin

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