The Proteomic Landscape of Parkin-Deficient and Parkin-Overexpressing Rat Nucleus Accumbens: An Insight into the Role of Parkin in Methamphetamine Use Disorder
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...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/15/7/958 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850077693685530624 |
|---|---|
| author | Akhil Sharma Tarek Atasi Florine Collin Weiwei Wang TuKiet T. Lam Rolando Garcia-Milian Tasnim Arroum Lucynda Pham Maik Hüttemann Anna Moszczynska |
| author_facet | Akhil Sharma Tarek Atasi Florine Collin Weiwei Wang TuKiet T. Lam Rolando Garcia-Milian Tasnim Arroum Lucynda Pham Maik Hüttemann Anna Moszczynska |
| author_sort | Akhil Sharma |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4ff76587476c44179d9e64b41c7a7cee |
| institution | DOAJ |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-4ff76587476c44179d9e64b41c7a7cee2025-08-20T02:45:45ZengMDPI AGBiomolecules2218-273X2025-07-0115795810.3390/biom15070958The Proteomic Landscape of Parkin-Deficient and Parkin-Overexpressing Rat Nucleus Accumbens: An Insight into the Role of Parkin in Methamphetamine Use DisorderAkhil Sharma0Tarek Atasi1Florine Collin2Weiwei Wang3TuKiet T. Lam4Rolando Garcia-Milian5Tasnim Arroum6Lucynda Pham7Maik Hüttemann8Anna Moszczynska9Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48202, USADepartment of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48202, USADepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USADepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USADepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USAHarvey Cushing/John Hay Whitney Medical Library, Yale University, New Haven, CT 06520, USACenter for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USACenter for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USACenter for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USADepartment of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48202, USAIn 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.https://www.mdpi.com/2218-273X/15/7/958parkinproteomenucleus accumbensmitochondriamethamphetamine |
| spellingShingle | Akhil Sharma Tarek Atasi Florine Collin Weiwei Wang TuKiet T. Lam Rolando Garcia-Milian Tasnim Arroum Lucynda Pham Maik Hüttemann Anna Moszczynska The Proteomic Landscape of Parkin-Deficient and Parkin-Overexpressing Rat Nucleus Accumbens: An Insight into the Role of Parkin in Methamphetamine Use Disorder Biomolecules parkin proteome nucleus accumbens mitochondria methamphetamine |
| title | The Proteomic Landscape of Parkin-Deficient and Parkin-Overexpressing Rat Nucleus Accumbens: An Insight into the Role of Parkin in Methamphetamine Use Disorder |
| title_full | The Proteomic Landscape of Parkin-Deficient and Parkin-Overexpressing Rat Nucleus Accumbens: An Insight into the Role of Parkin in Methamphetamine Use Disorder |
| title_fullStr | The Proteomic Landscape of Parkin-Deficient and Parkin-Overexpressing Rat Nucleus Accumbens: An Insight into the Role of Parkin in Methamphetamine Use Disorder |
| title_full_unstemmed | The Proteomic Landscape of Parkin-Deficient and Parkin-Overexpressing Rat Nucleus Accumbens: An Insight into the Role of Parkin in Methamphetamine Use Disorder |
| title_short | The Proteomic Landscape of Parkin-Deficient and Parkin-Overexpressing Rat Nucleus Accumbens: An Insight into the Role of Parkin in Methamphetamine Use Disorder |
| title_sort | proteomic landscape of parkin deficient and parkin overexpressing rat nucleus accumbens an insight into the role of parkin in methamphetamine use disorder |
| topic | parkin proteome nucleus accumbens mitochondria methamphetamine |
| url | https://www.mdpi.com/2218-273X/15/7/958 |
| work_keys_str_mv | AT akhilsharma theproteomiclandscapeofparkindeficientandparkinoverexpressingratnucleusaccumbensaninsightintotheroleofparkininmethamphetamineusedisorder AT tarekatasi theproteomiclandscapeofparkindeficientandparkinoverexpressingratnucleusaccumbensaninsightintotheroleofparkininmethamphetamineusedisorder AT florinecollin theproteomiclandscapeofparkindeficientandparkinoverexpressingratnucleusaccumbensaninsightintotheroleofparkininmethamphetamineusedisorder AT weiweiwang theproteomiclandscapeofparkindeficientandparkinoverexpressingratnucleusaccumbensaninsightintotheroleofparkininmethamphetamineusedisorder AT tukiettlam theproteomiclandscapeofparkindeficientandparkinoverexpressingratnucleusaccumbensaninsightintotheroleofparkininmethamphetamineusedisorder AT rolandogarciamilian theproteomiclandscapeofparkindeficientandparkinoverexpressingratnucleusaccumbensaninsightintotheroleofparkininmethamphetamineusedisorder AT tasnimarroum theproteomiclandscapeofparkindeficientandparkinoverexpressingratnucleusaccumbensaninsightintotheroleofparkininmethamphetamineusedisorder AT lucyndapham theproteomiclandscapeofparkindeficientandparkinoverexpressingratnucleusaccumbensaninsightintotheroleofparkininmethamphetamineusedisorder AT maikhuttemann theproteomiclandscapeofparkindeficientandparkinoverexpressingratnucleusaccumbensaninsightintotheroleofparkininmethamphetamineusedisorder AT annamoszczynska theproteomiclandscapeofparkindeficientandparkinoverexpressingratnucleusaccumbensaninsightintotheroleofparkininmethamphetamineusedisorder AT akhilsharma proteomiclandscapeofparkindeficientandparkinoverexpressingratnucleusaccumbensaninsightintotheroleofparkininmethamphetamineusedisorder AT tarekatasi proteomiclandscapeofparkindeficientandparkinoverexpressingratnucleusaccumbensaninsightintotheroleofparkininmethamphetamineusedisorder AT florinecollin proteomiclandscapeofparkindeficientandparkinoverexpressingratnucleusaccumbensaninsightintotheroleofparkininmethamphetamineusedisorder AT weiweiwang proteomiclandscapeofparkindeficientandparkinoverexpressingratnucleusaccumbensaninsightintotheroleofparkininmethamphetamineusedisorder AT tukiettlam proteomiclandscapeofparkindeficientandparkinoverexpressingratnucleusaccumbensaninsightintotheroleofparkininmethamphetamineusedisorder AT rolandogarciamilian proteomiclandscapeofparkindeficientandparkinoverexpressingratnucleusaccumbensaninsightintotheroleofparkininmethamphetamineusedisorder AT tasnimarroum proteomiclandscapeofparkindeficientandparkinoverexpressingratnucleusaccumbensaninsightintotheroleofparkininmethamphetamineusedisorder AT lucyndapham proteomiclandscapeofparkindeficientandparkinoverexpressingratnucleusaccumbensaninsightintotheroleofparkininmethamphetamineusedisorder AT maikhuttemann proteomiclandscapeofparkindeficientandparkinoverexpressingratnucleusaccumbensaninsightintotheroleofparkininmethamphetamineusedisorder AT annamoszczynska proteomiclandscapeofparkindeficientandparkinoverexpressingratnucleusaccumbensaninsightintotheroleofparkininmethamphetamineusedisorder |