Abstract：Alzheimer′s disease (AD) is a chronic, progressive neurodegenerative disease, and oxidative stress injury and toxic aldehydes deposition play an important role in AD pathology. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is an aldehyde oxidation-reduction enzyme. ALDH2 activity is determined by its genotype. Carriers of ALDH2 mutation have a higher risk of suffering AD. Basic studies suggest that ALDH2 can reduce the deposition of 4-HNE produced by oxidative stress in important organs, especially brain tissues, thereby reducing the oxidative stress injury of neuronal cells. This article will review the research progress of ALDH2 in AD, and provide novel insights for disease prevention and control.
刘海涛 葛伟. 乙醛脱氢酶2在阿尔茨海默病中的研究进展[J]. 中国医药导报, 2020, 17(4): 36-39.
LIU Haitao GE Wei. Research progress of aldehyde dehydrogenase 2 in Alzheimer′s disease. 中国医药导报, 2020, 17(4): 36-39.
[1] Kanamaru T，Kamimura N，Yokota T，et al. Oxidative stress accelerates amyloid deposition and memory impairment in a double-transgenic mouse model of Alzheimer′s disease [J]. Neurosci Lett，2015，587：126-131.
[2] Grunblatt E，Riederer P. Aldehyde dehydrogenase （ALDH） in Alzheimer′s and Parkinson′s disease [J]. J Neural Transm（Vienna），2016，123（2）：83-90.
[3] Nichols E，Szoeke CEI，Vollset SE，et al. Global，regional，and national burden of Alzheimer′s disease and other dementias，1990-2016：a systematic analysis for the global burden of disease study 2016 [J]. Lancet Neurol，2019，18（1）：88-106.
[4] Tublin JM，Adelstein JM，Del Monte F，et al. Getting to the heart of Alzheimer disease [J]. Circ Res，2019，124（1）：142-149.
[5] Chen CH，Joshi AU，Mochly-Rosen D. The role of mitochondrial aldehyde dehydrogenase 2 （ALDH2） in neuropathology and neurodegeneration [J]. Acta Neurol Taiwan，2016，25（4）：111-123.
[6] Chen CH，Ferreira JC，Gross ER，et al. Targeting aldehyde dehydrogenase 2：new therapeutic opportunities [J]. Physiol Rev，2014，94（1）：1-34.
[7] Li H，Borinskaya S，Yoshimura K，et al. Refined geographic distribution of the oriental ALDH2*504Lys （nee 487Lys） variant [J]. Ann Hum Genet，2009，73（Pt 3）：335-345.
[8] Munzel T，Daiber A. The potential of aldehyde dehydrogenase 2 as a therapeutic target in cardiovascular disease [J]. Expert Opin Ther Targets，2018，22（3）：217-231.
[9] Zhao Y，Wang C. Glu504Lys single nucleotide polymorphism of aldehyde dehydrogenase 2 gene and the risk of human diseases [J]. Biomed Res Int，2015，2015：1-9.
[10] Nesi G，Sestito S，Digiacomo M，et al. Oxidative stress，mitochondrial abnormalities and proteins deposition：multitarget approaches in Alzheimer′s disease [J]. Curr Top Med Chem，2017，17（27）：3062-3079.
[11] Zhang WY，Wang KY，Li YJ，et al. Chronic stress causes protein kinase C epsilon-aldehyde dehydrogenase 2 signaling pathway perturbation in the rat hippocampus and prefrontal cortex，but not in the myocardium [J]. Neural Regen Res，2018，13（7）：1225-1230.
[12] Sinharoy P，McAllister SL，Vasu M，et al. Environmental aldehyde sources and the health implications of exposure [J]. Adv Exp Med Biol，2019，1193：35-52.
[13] Breitzig M，Bhimineni C，Lockey R，et al. 4-Hydroxy-2-nonenal：a critical target in oxidative stress? [J]. Am J Physiol Cell Physiol，2016，311（4）：C537-C543.
[14] Mol M，Regazzoni L，Altomare A，et al. Enzymatic and non-enzymatic detoxification of 4-hydroxynonenal：methodological aspects and biological consequences [J]. Free Radic Biol Med，2017，111：328-344.
[15] Xue L，Yang F，Han Z，et al. ALDH2 mediates the dose-response protection of chronic ethanol against endothelial senescence through SIRT1/p53 pathway [J]. Biochem Biophys Res Commun，2018，504（4）：777-783.
[16] Ma L，Lu ZN. Role of ADH1B rs1229984 and ALDH2 rs671 gene polymorphisms in the development of Alzheimer′s disease [J]. Genet Mol Res，2016，15（4）：5-12.
[17] Komatsu M，Shibata N，Ohnuma T，et al. Polymorphisms in the aldehyde dehydrogenase 2 and dopamine beta hydroxylase genes are not associated with Alzheimer′s disease [J]. J Neural Transm（Vienna），2014，121（4）：427-432.
[18] Chen J，Huang W，Cheng CH，et al. Association between aldehyde dehydrogenase-2 polymorphisms and risk of Alzheimer′s disease and Parkinson′s disease：a meta-analysis based on 5315 individuals [J]. Front Neurol，2019，10：290-299.
[19] Chen Y，Zhou CF，Xiao F，et al. Inhibition of ALDH2 protects PC12 cells against formaldehyde-induced cytotoxicity：involving the protection of hydrogen sulphide [J]. Clin Exp Pharmacol Physiol，2017，44（5）：595-601.
[20] Tanaka K，Whelan KA，Chandramouleeswaran PM，et al. ALDH2 modulates autophagy flux to regulate acetaldehyde-mediated toxicity thresholds [J]. Am J Cancer Res，2016，6（4）：781-796.
[21] Ohsawa I，Nishimaki K，Murakami Y，et al. Age-dependent neurodegeneration accompanying memory loss in transgenic mice defective in mitochondrial aldehyde dehydrogenase 2 activity [J]. J Neurosci，2008，28（24）：6239-6249.
[22] Krzyzanowska A，Garcia-Consuegra I，Pascual C，et al. Expression of regulatory proteins in choroid plexus changes in early stages of Alzheimer disease [J]. J Neuropathol Exp Neurol，2015，74（4）：359-369.
[23] D′Souza Y，Elharram A，Soon-Shiong R，et al. Characterization of Aldh2-/- mice as an age-related model of cognitive impairment and Alzheimer′s disease [J]. Mol Brain，2015，8：27-42.
[24] Grinan-Ferre C，Sarroca S，Ivanova A，et al. Epigenetic mechanisms underlying cognitive impairment and Alzh-eimer disease hallmarks in 5XFAD mice [J]. Aging（Albany NY），2016，8（4）：664-684.
[25] Li M，Zhang P，Wei HJ，et al. Hydrogen sulfide ameliorates homocysteine-induced cognitive dysfunction by inhibition of reactive aldehydes involving upregulation of ALDH2 [J]. Int J Neuropsychopharmacol，2017，20（4）：305-315.
[26] Puigoriol-Illamola D，Grinan-Ferre C，Vasilopoulou F，et al. 11beta-HSD1 inhibition by RL-118 promotes autophagy and correlates with reduced oxidative stress and inflammation，enhancing cognitive performance in SAMP8 mouse model [J]. Mol Neurobiol，2018，55（12）：8904-8915.
[27] Stachowicz A，Olszanecki R，Suski M，et al. Proteomic analysis of mitochondria-enriched fraction isolated from the frontal cortex and hippocampus of apolipoprotein e knockout mice treated with Alda-1， an activator of mitochondrial aldehyde dehydrogenase（ALDH2）[J]. Int J Mol Sci，2017，18（2）：435-450.
[28] Solito R，Corti F，Chen CH，et al. Mitochondrial aldehyde dehydrogenase-2 activation prevents beta-amyloid-induced endothelial cell dysfunction and restores angiogenesis [J]. J Cell Sci，2013，126（Pt 9）：1952-1961.
[29] Luo J，Lee SH，VandeVrede L，et al. A multifunctional therapeutic approach to disease modification in multiple familial mouse models and a novel sporadic model of Alzheimer′s disease [J]. Mol Neurodegener，2016，11：35-48.
2020, Vol. 17 
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