Effects of “Essential AD2” Supplement on Blood Acetaldehyde Levels in Individuals Who Have Aldehyde Dehydrogenase (ALDH2) Deficiency

Fujioka, Ken; Gordon, Spencer

doi:10.1097/mjt.0000000000000744

Cited by 7 publications

(11 citation statements)

References 10 publications

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“…A proteomic study showed that the PDIA3 protein is involved in Aβ-stimulated microglial activation ( 26 ). The ALDH2 gene encoding glyoxylate dehydrogenase 2 is involved in the biological process of maintaining the mitochondrial function, and memory impairment occurred in ALDH2 knockout mice ( 27 ). Except for these aforementioned genes, CD247 , CD3D , CD3G , PTPN6 , ZAP70 , CALR , IL7R , YWHAQ , EZR , MSN , PGD , and TKT have not been reported to be associated with AD.…”

Section: Discussionmentioning

confidence: 99%

Single-Cell RNA Sequencing of Peripheral Blood Reveals Immune Cell Signatures in Alzheimer’s Disease

Jia

2021

Front. Immunol.

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The peripheral immune system is thought to affect the pathology of the central nervous system in Alzheimer’s disease (AD). However, current knowledge is inadequate for understanding the characteristics of peripheral immune cells in AD. This study aimed to explore the molecular basis of peripheral immune cells and the features of adaptive immune repertoire at a single cell level. We profiled 36,849 peripheral blood mononuclear cells from AD patients with amyloid-positive status and normal controls with amyloid-negative status by 5’ single-cell transcriptome and immune repertoire sequencing using the cell ranger standard analysis procedure. We revealed five immune cell subsets: CD4+ T cells, CD8+ T cells, B cells, natural killer cells, and monocytes–macrophages cells, and disentangled the characteristic alterations of cell subset proportion and gene expression patterns in AD. Thirty-one cell type-specific key genes, comprising abundant human leukocyte antigen genes, and multiple immune-related pathways were identified by protein–protein interaction network and pathway enrichment analysis. We also found high-frequency amplification clonotypes in T and B cells and decreased diversity in T cells in AD. As clone amplification suggested the activation of an adaptive immune response against specific antigens, we speculated that the peripheral adaptive immune response, especially mediated by T cells, may have a role in the pathogenesis of AD. This finding may also contribute to further research regarding disease mechanism and the development of immune-related biomarkers or therapy.

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Section: Discussionmentioning

confidence: 99%

Single-Cell RNA Sequencing of Peripheral Blood Reveals Immune Cell Signatures in Alzheimer’s Disease

Jia

2021

Front. Immunol.

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“…Other than the use of nutritional supplements, 28 no therapies are available to treat ALDH2 deficiency. While scaling from mice to humans has many challenges, the data in the present study supports the concept that AAV-mediated gene therapy represents a possible effective therapy for the ALDH2 deficiency state.…”

Section: Discussionmentioning

confidence: 99%

Gene Therapy Correction of Aldehyde Dehydrogenase 2 Deficiency

Matsumura

Stiles

Reid

et al. 2019

Molecular Therapy - Methods & Clinical Development

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Aldehyde dehydrogenase 2 (ALDH2) deficiency causes “Asian flush syndrome,” presenting as alcohol-induced facial flushing, tachycardia, nausea, and headaches. One of the most common hereditary enzyme deficiencies, it affects 35%–40% of East Asians and 8% of the world population. ALDH2 is the key enzyme in ethanol metabolism; with ethanol challenge, the common ALDH2*2 (E487K) mutation results in accumulation of toxic acetaldehyde. ALDH2*2 heterozygotes have increased risk for upper digestive tract cancers, compounded by smoking and drinking alcohol. We hypothesized that a one-time administration of an adeno-associated virus (AAV) gene transfer vector expressing the human ALDH2 coding sequence (AAVrh.10hALDH2) would correct the deficiency state. AAVrh.10hALDH2 was administered intravenously to Aldh2 knockout (Aldh2−/−) and Aldh2 E487K knockin homozygous (Aldh2E487K+/+) mice. Following acute ethanol ingestion, untreated ALDH2-deficient mice had elevated acetaldehyde levels and performed poorly in behavioral tests. In contrast, treated Aldh2−/− and Aldh2E487K+/+ mice had lower serum acetaldehyde levels and improved behavior. Thus, in vivo AAV-mediated ALDH2 therapy may reverse the deficiency state in ALDH2*2 individuals, eliminating the Asian flush syndrome and reducing the risk for associated disorders.

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“…This is also the case with CSA, which is a common disease among East Asians [ 73 ]. A mutation in the ALDH2 gene is believed to be the cause of this condition; moreover, it is likely that nearly 1 billion people worldwide carry the mutation, most of whom are Easterners [ 74 ]. It has been suggested that the risk of coronary heart disease and myocardial infarction may be increased due to the Glu504Lys variant in the ALDH2 gene, which is responsible for reducing the ability of ALDH2 to metabolize acetaldehyde [ 72 ].…”

Section: Deficient Aldehyde Dehydrogenase 2 Activitymentioning

confidence: 99%

Cellular Mechanisms of Coronary Artery Spasm

et al. 2022

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Coronary artery spasm (CAS) is a reversible phenomenon caused by spontaneous excessive vascular smooth muscle contractility and vascular wall hypertonicity, which results in partial or complete closure of the lumen of normal or atherosclerotic coronary arteries. The clinical picture of CAS includes chest discomfort which is similar in quality to that of stable effort angina. Mechanisms underlying the development of CAS are still unclear. CAS certainly is a multifactorial disease. In this review, we paid attention to the role of the main pathophysiologic mechanisms in CAS: endothelial dysfunction, chronic inflammation, oxidative stress, smooth muscle hypercontractility, atherosclerosis and thrombosis, and mutations leading to deficient aldehyde dehydrogenase 2 (ALDH2) activity. These findings might shed novel insight on the underlying mechanisms and identify potential diagnostic and therapeutic targets for cardiovascular diseases in the future.

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Effects of “Essential AD2” Supplement on Blood Acetaldehyde Levels in Individuals Who Have Aldehyde Dehydrogenase (ALDH2) Deficiency

Cited by 7 publications

References 10 publications

Single-Cell RNA Sequencing of Peripheral Blood Reveals Immune Cell Signatures in Alzheimer’s Disease

Single-Cell RNA Sequencing of Peripheral Blood Reveals Immune Cell Signatures in Alzheimer’s Disease

Gene Therapy Correction of Aldehyde Dehydrogenase 2 Deficiency

Cellular Mechanisms of Coronary Artery Spasm

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