Pharmacoproteomics Profile in Response to Acamprosate Treatment of an Alcoholism Animal Model

Reker, Ashlie N.; Hinton, David J.; Oliveros, Alfredo; Shen, Xinggui; Andres-Beck, Lindsey G.; Wininger, Katheryn; Trutschl, Marjan; Cvek, Urška; Choi, Doo Sup; Nam, Hyung Wook

doi:10.1002/pmic.201700417

Cited by 10 publications

(7 citation statements)

References 51 publications

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“…by acamprosate (Frye et al, 2016;Umhau et al, 2010), another medication for AUD that may also act through neuroimmune mechanisms (Germany et al, 2018). Studies suggest that ibudilast may work similar to protect against the hyper-glutamatergic state and maintain glutamate homeostasis in the brain (Bachtell et al, 2017;Tominaga et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Ibudilast attenuates alcohol cue–elicited frontostriatal functional connectivity in alcohol use disorder

Burnette

Ray

Irwin

et al. 2021

Alcoholism Clin & Exp Res

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Alcohol use disorder (AUD) is a highly prevalent chronic relapsing disorder (Grant et al., 2015); however, it is among the most undertreated health conditions (Carvalho et al., 2019), with only 7% of adults with AUD receiving treatment (Hasin et al., 2007). The Food and Drug Administration has approved only 4 pharmacotherapies for the treatment of AUD to date, and these medications are limited in efficacy (Ray et al., 2019). There is a great need to develop new and more effective treatments for AUD, with a specific focus on novel molecular targets (Litten et al., 2012(Litten et al., , 2016.One such novel pharmacotherapy is ibudilast (IBUD; also known as MN-166, previously AV411 and available as Ketas in Japan for the treatment of bronchial asthma and for cerebrovascular disorders).

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Section: Discussionmentioning

confidence: 99%

Ibudilast attenuates alcohol cue–elicited frontostriatal functional connectivity in alcohol use disorder

Burnette

Ray

Irwin

et al. 2021

Alcoholism Clin & Exp Res

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“…Specificity of the primary antibodies has been tested using Western blotting (Supplementary Figure 1A) and reported previously (Simpson et al, 2010;Yao et al, 2015;Wang et al, 2017;Germany et al, 2018;Bacci et al, 2019;Castaneda-Cabral et al, 2020;Li et al, 2020;Wilkie et al, 2020;Yoshino et al, 2020). Western blotting was performed as described by Kwakowsky et al (2018).…”

Section: Western Blottingmentioning

confidence: 99%

EAAT2 Expression in the Hippocampus, Subiculum, Entorhinal Cortex and Superior Temporal Gyrus in Alzheimer’s Disease

Yeung

Palpagama

Wood

et al. 2021

Front. Cell. Neurosci.

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Alzheimer’s disease (AD) is a neuropathological disorder characterized by the presence and accumulation of amyloid-beta plaques and neurofibrillary tangles. Glutamate dysregulation and the concept of glutamatergic excitotoxicity have been frequently described in the pathogenesis of a variety of neurodegenerative disorders and are postulated to play a major role in the progression of AD. In particular, alterations in homeostatic mechanisms, such as glutamate uptake, have been implicated in AD. An association with excitatory amino acid transporter 2 (EAAT2), the main glutamate uptake transporter, dysfunction has also been described. Several animal and few human studies examined EAAT2 expression in multiple brain regions in AD but studies of the hippocampus, the most severely affected brain region, are scarce. Therefore, this study aims to assess alterations in the expression of EAAT2 qualitatively and quantitatively through DAB immunohistochemistry (IHC) and immunofluorescence within the hippocampus, subiculum, entorhinal cortex, and superior temporal gyrus (STG) regions, between human AD and control cases. Although no significant EAAT2 density changes were observed between control and AD cases, there appeared to be increased transporter expression most likely localized to fine astrocytic branches in the neuropil as seen on both DAB IHC and immunofluorescence. Therefore, individual astrocytes are not outlined by EAAT2 staining and are not easily recognizable in the CA1–3 and dentate gyrus regions of AD cases, but the altered expression patterns observed between AD and control hippocampal cases could indicate alterations in glutamate recycling and potentially disturbed glutamatergic homeostasis. In conclusion, no significant EAAT2 density changes were found between control and AD cases, but the observed spatial differences in transporter expression and their functional significance will have to be further explored.

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“…Studies for non‐cancer‐related therapeutics emerged as well. Germany et al recently studied the mechanism of ineffectiveness of Acamprosate, an FDA‐approved agent for alcoholism treatment (Germany et al, ). Using MS1 intensity‐based quantification method, a total of 3,634 proteins were quantified in 16 patient samples.…”

Section: Applications Of Ms1‐based Quantification In Relatively Largementioning

confidence: 99%

MS1 ion current‐based quantitative proteomics: A promising solution for reliable analysis of large biological cohorts

Wang¹,

Shen²,

Rasam

et al. 2019

Mass Spectrometry Reviews

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The rapidly‐advancing field of pharmaceutical and clinical research calls for systematic, molecular‐level characterization of complex biological systems. To this end, quantitative proteomics represents a powerful tool but an optimal solution for reliable large‐cohort proteomics analysis, as frequently involved in pharmaceutical/clinical investigations, is urgently needed. Large‐cohort analysis remains challenging owing to the deteriorating quantitative quality and snowballing missing data and false‐positive discovery of altered proteins when sample size increases. MS1 ion current‐based methods, which have become an important class of label‐free quantification techniques during the past decade, show considerable potential to achieve reproducible protein measurements in large cohorts with high quantitative accuracy/precision. Nonetheless, in order to fully unleash this potential, several critical prerequisites should be met. Here we provide an overview of the rationale of MS1‐based strategies and then important considerations for experimental and data processing techniques, with the emphasis on (i) efficient and reproducible sample preparation and LC separation; (ii) sensitive, selective and high‐resolution MS detection; iii)accurate chromatographic alignment; (iv) sensitive and selective generation of quantitative features; and (v) optimal post‐feature‐generation data quality control. Prominent technical developments in these aspects are discussed. Finally, we reviewed applications of MS1‐based strategy in disease mechanism studies, biomarker discovery, and pharmaceutical investigations.

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Pharmacoproteomics Profile in Response to Acamprosate Treatment of an Alcoholism Animal Model

Cited by 10 publications

References 51 publications

Ibudilast attenuates alcohol cue–elicited frontostriatal functional connectivity in alcohol use disorder

Ibudilast attenuates alcohol cue–elicited frontostriatal functional connectivity in alcohol use disorder

EAAT2 Expression in the Hippocampus, Subiculum, Entorhinal Cortex and Superior Temporal Gyrus in Alzheimer’s Disease

MS1 ion current‐based quantitative proteomics: A promising solution for reliable analysis of large biological cohorts

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