Aldehyde dehydrogenase 2 in the spotlight: The link between mitochondria and neurodegeneration

Deza-Ponzio, Romina; Herrera, Macarena Lorena; Bellini, María José; Virgolini, Miriam Beatríz; Hereñú, Claudia Beatriz

doi:10.1016/j.neuro.2018.06.005

Cited by 46 publications

(31 citation statements)

References 67 publications

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“…While this is the first report linking PI16 with any neurodegenerative process, mitochondrial ALDH1B1 plays a crucial role concerning the oxidative metabolism of toxic aldehydes in the brain. Thus, the alteration of ALDH1B1 in the OB together with the recent emerging evidence for ALDH2 stands for its implication in the process of neurodegeneration [ 48 ].…”

Section: Resultsmentioning

confidence: 99%

Proteomic Characterization of the Olfactory Molecular Imbalance in Dementia with Lewy Bodies

Lachén-Montes

Mendizuri

Schvartz

et al. 2020

IJMS

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Olfactory dysfunction is one of the prodromal symptoms in dementia with Lewy bodies (DLB). However, the molecular pathogenesis associated with decreased smell function remains largely undeciphered. We generated quantitative proteome maps to detect molecular alterations in olfactory bulbs (OB) derived from DLB subjects compared to neurologically intact controls. A total of 3214 olfactory proteins were quantified, and 99 proteins showed significant alterations in DLB cases. Protein interaction networks disrupted in DLB indicated an imbalance in translation and the synaptic vesicle cycle. These alterations were accompanied by alterations in AKT/MAPK/SEK1/p38 MAPK signaling pathways that showed a distinct expression profile across the OB–olfactory tract (OT) axis. Taken together, our data partially reflect the missing links in the biochemical understanding of olfactory dysfunction in DLB.

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Section: Resultsmentioning

confidence: 99%

Proteomic Characterization of the Olfactory Molecular Imbalance in Dementia with Lewy Bodies

Lachén-Montes

Mendizuri

Schvartz

et al. 2020

IJMS

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“…OLFM1, olfactomedin 1, participates in axon guidance and growth (110,111). ALDH2, aldehyde dehydrogenase is a mitochondrial enzyme crucial for metabolism of toxic aldehydes in the brain, such as catecholaminergic metabolites (112) and is elevated in Alzheimer's brain putamen (113). ATP1A1 is a Na ϩ /K ϩ -ATPase for cation transport important for membrane potential and electrical excitability of neurons (114).…”

Section: Molecular and Cellular Proteomics 196 1021mentioning

confidence: 99%

Dysregulation of Exosome Cargo by Mutant Tau Expressed in Human-induced Pluripotent Stem Cell (iPSC) Neurons Revealed by Proteomics Analyses

Podvin

Jones

Liu

et al. 2020

Molecular & Cellular Proteomics

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Accumulation and propagation of hyperphosphorylated Tau (p-Tau) is a common neuropathological hallmark associated with neurodegeneration of Alzheimer's disease (AD), frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), and related tauopathies. Extracellular vesicles, specifically exosomes, have recently been demonstrated to participate in mediating Tau propagation in brain. Exosomes produced by human induced pluripotent stem cell (iPSC)-derived neurons expressing mutant Tau (mTau), containing the P301L and V337M Tau mutations of FTDP-17, possess the ability to propagate p-Tau pathology after injection into mouse brain. To gain an understanding of the mTau exosome cargo involved in Tau pathogenesis, these pathogenic exosomes were analyzed by proteomics and bioinformatics. The data showed that mTau expression dysregulates the exosome proteome to result in 1) proteins uniquely present only in mTau, and not control exosomes, 2) the absence of proteins in mTau exosomes, uniquely present in control exosomes, and 3) shared proteins which were significantly upregulated or downregulated in mTau compared with control exosomes. Notably, mTau exosomes (not control exosomes) contain ANP32A (also known as I1PP2A), an endogenous inhibitor of the PP2A phosphatase which regulates the phosphorylation state of p-Tau. Several of the mTau exosome-specific proteins have been shown to participate in AD mechanisms involving lysosomes, inflammation, secretases, and related processes. Furthermore, the mTau exosomes lacked a substantial portion of proteins present in control exosomes involved in pathways of localization, vesicle transport, and protein binding functions. The shared proteins present in both mTau and control exosomes represented exosome functions of vesicle-mediated transport, exocytosis, and secretion processes. These data illustrate mTau as a dynamic regulator of the biogenesis of exosomes to result in acquisition, deletion, and up- or downregulation of protein cargo to result in pathogenic mTau exosomes capable of in vivo propagation of p-Tau neuropathology in mouse brain.

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“…Acetaldehyde dehydrogenase 2 is a rate-limiting enzyme for alcohol metabolism, which has been shown to exert neuroprotective effects (Deza-Ponzio et al, 2018). In retinas of STZ rats, it has been reported to promote antioxidant enzyme activity, reduce the expression of proinflammatory cytokines, ameliorate ERG, and significantly reduce VEGF expression (He et al, 2018).…”

Section: Other Factorsmentioning

confidence: 99%

Relationships Between Neurodegeneration and Vascular Damage in Diabetic Retinopathy

2019

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Diabetic retinopathy (DR) is a common complication of diabetes and constitutes a major cause of vision impairment and blindness in the world. DR has long been described exclusively as a microvascular disease of the eye. However, in recent years, a growing interest has been focused on the contribution of neuroretinal degeneration to the pathogenesis of the disease, and there are observations suggesting that neuronal death in the early phases of DR may favor the development of microvascular abnormalities, followed by the full manifestation of the disease. However, the mediators that are involved in the crosslink between neurodegeneration and vascular changes have not yet been identified. According to our hypothesis, vascular endothelial growth factor (VEGF) could probably be the most important connecting link between the death of retinal neurons and the occurrence of microvascular lesions. Indeed, VEGF is known to play important neuroprotective actions; therefore, in the early phases of DR, it may be released in response to neuronal suffering, and it would act as a double-edged weapon inducing both neuroprotective and vasoactive effects. If this hypothesis is correct, then any retinal stress causing neuronal damage should be accompanied by VEGF upregulation and by vascular changes. Similarly, any compound with neuroprotective properties should also induce VEGF downregulation and amelioration of the vascular lesions. In this review, we searched for a correlation between neurodegeneration and vasculopathy in animal models of retinal diseases, examining the effects of different neuroprotective substances, ranging from nutraceuticals to antioxidants to neuropeptides and others and showing that reducing neuronal suffering also prevents overexpression of VEGF and vascular complications. Taken together, the reviewed evidence highlights the crucial role played by mediators such as VEGF in the relationship between retinal neuronal damage and vascular alterations and suggests that the use of neuroprotective substances could be an efficient strategy to prevent the onset or to retard the development of DR.

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Aldehyde dehydrogenase 2 in the spotlight: The link between mitochondria and neurodegeneration

Cited by 46 publications

References 67 publications

Proteomic Characterization of the Olfactory Molecular Imbalance in Dementia with Lewy Bodies

Proteomic Characterization of the Olfactory Molecular Imbalance in Dementia with Lewy Bodies

Dysregulation of Exosome Cargo by Mutant Tau Expressed in Human-induced Pluripotent Stem Cell (iPSC) Neurons Revealed by Proteomics Analyses

Relationships Between Neurodegeneration and Vascular Damage in Diabetic Retinopathy

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