The Proteomic Landscape of Parkin-Deficient and Parkin-Overexpressing Rat Nucleus Accumbens: An Insight into the Role of Parkin in Methamphetamine Use Disorder.

IF 4.8 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomolecules Pub Date : 2025-07-03 DOI:10.3390/biom15070958

Akhil Sharma, Tarek Atasi, Florine Collin, Weiwei Wang, TuKiet T Lam, Rolando Garcia-Milian, Tasnim Arroum, Lucynda Pham, Maik Hüttemann, Anna Moszczynska

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Abstract

In recent years, methamphetamine (METH) misuse in the US has been rapidly increasing, and there is no FDA-approved pharmacotherapy for METH use disorder (MUD). We previously determined that ubiquitin-protein ligase parkin is involved in the regulation of METH addictive behaviors in rat models of MUD. Parkin is not yet a "druggable" drug target; therefore, this study aimed to determine which biological processes, pathways, and proteins downstream of parkin are likely drug targets against MUD. Employing young adult Long Evans male rats with parkin deficit or excess in the nucleus accumbens (NAc), label-free proteomics, and molecular biology, we determined that the pathways downstream of parkin that are candidates for regulating METH addictive behaviors in young adult male rats are mitochondrial respiration, oxidative stress, AMPA receptor trafficking, GABAergic neurotransmission, and actin cytoskeleton dynamics.

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Parkin缺乏和过表达大鼠伏隔核的蛋白质组学景观：Parkin在甲基苯丙胺使用障碍中的作用。

近年来，甲基苯丙胺（METH）滥用在美国迅速增加，并且没有fda批准的药物治疗甲基苯丙胺使用障碍（MUD）。我们之前确定泛素蛋白连接酶帕金参与了大鼠MUD模型中甲基苯丙胺成瘾行为的调节。帕金森氏还不是一个“可用药”的药物靶点；因此，本研究旨在确定parkin下游的哪些生物过程、途径和蛋白质可能是针对MUD的药物靶点。利用伏隔核（NAc）帕金缺失或过量的年轻成年Long Evans雄性大鼠，通过无标记蛋白质组学和分子生物学，我们确定了帕金下游的途径是调节年轻成年雄性大鼠甲基安非他明成瘾行为的候选途径，包括线粒体呼吸、氧化应激、AMPA受体运输、gaba能神经传递和肌动蛋白细胞骨架动力学。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomolecules Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

9.40

自引率

3.60%

发文量

1640

审稿时长

18.28 days

期刊介绍： Biomolecules (ISSN 2218-273X) is an international, peer-reviewed open access journal focusing on biogenic substances and their biological functions, structures, interactions with other molecules, and their microenvironment as well as biological systems. Biomolecules publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.