Article
Neurosciences
Zijuan Zhang, Hai Li, Yunfang Su, Jinlian Ma, Ye Yuan, Ziyang Yu, Ming Shi, Simai Shao, Zhenqiang Zhang, Christian Holscher
Summary: Research demonstrates that the CCK analogue has neuroprotective effects and improves locomotor function in an acute PD mouse model. It acts by restoring dopaminergic neuron count and synapse number, reducing neuroinflammation and autophagy impairment, and protecting against mitochondrial and ER damage.
FRONTIERS IN NEUROSCIENCE
(2022)
Review
Behavioral Sciences
Abdolvahed Narmashiri, Mojtaba Abbaszadeh, Ali Ghazizadeh
Summary: This article provides a comprehensive review and meta-analysis on the effects of MPTP on memory and motor functions in Parkinson's disease. The results show that MPTP not only significantly affects motor functions, but also various mnemonic processes. However, no systematic relationship between the MPTP injection protocol parameters and the extent of induced PD symptoms was found.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2022)
Article
Multidisciplinary Sciences
Khairiah Razali, Mohd Hamzah Mohd Nasir, Noratikah Othman, Abd Almonem Doolaanea, Jaya Kumar, Wisam Nabeel Ibrahim, Wael M. Y. Mohamed
Summary: Parkinson's disease is a common brain motor disorder characterized by motor impairments. Research on the pathogenesis of PD is ongoing, and zebrafish has emerged as a useful model for studying PD. This study demonstrates the effects of MPTP on zebrafish swimming behavior and provides insights into the establishment of PD animal models.
Article
Neurosciences
Hairong Peng, Shui Yu, Yukai Zhang, Yanqing Yin, Jiawei Zhou
Summary: A wealth of evidence suggests that gastrointestinal dysfunction is associated with Parkinson's disease (PD), but the mechanisms are not well-defined. This study reveals the importance of intestinal dopamine D2 receptor (DRD2) activity and succinate from the gut microbiome in the survival of nigral dopaminergic neurons.
NEUROSCIENCE BULLETIN
(2022)
Article
Immunology
Hyongjun Jeon, Chang-Hwan Bae, Yukyoung Lee, Hee-Young Kim, Seungtae Kim
Summary: Korean red ginseng (KRG) has anti-inflammatory effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model, and can influence microbiome composition, thereby preventing dopaminergic neuronal death and expression of inflammatory factors.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Chemistry, Applied
Vincent M. Lombardo, Louise Bernier, Ming Z. Chen, William Farrell, Andrew Flick, Philippe Nuhant, Neal W. Sach, Yong Tao, John Trujillo
Summary: Chiral piperidines are commonly found in approved drugs and drug candidates, but their synthesis faces challenges of scalability and stereochemical control. This research focused on accessing stereochemically pure 3,4-disubstituted piperidines through a classical resolution method, which could have broader utility in pharmaceutical intermediates. The practical synthesis described in this work allows for the production of kilogram quantities of enantiopure precursor, enabling scale-up efforts for toxicology studies.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2021)
Article
Neurosciences
Eduard Bentea, Laura De Pauw, Lise Verbruggen, Lila C. Winfrey, Lauren Deneyer, Cynthia Moore, Giulia Albertini, Hideyo Sato, Ann Van Eeckhaut, Charles K. Meshul, Ann Massie
Summary: Our study revealed age-related protection against proteasome inhibition-induced nigrostriatal degeneration in xCT(-/-) mice, while xCT deletion failed to protect nigral dopaminergic neurons of aged mice against MPTP-induced toxicity. This provides new insights into the role of system x(c)(-) in mechanisms of dopaminergic cell loss and its interaction with aging.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Neurosciences
Adeola Oluwatosin Adedara, Guilherme Wildner, Julia Sepel Loreto, Matheus Mulling dos Santos, Amos Olalekan Abolaji, Nilda Vargas Barbosa
Summary: The study investigated the protective effects of kaempferol (KMP) against the toxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in Drosophila melanogaster. It was found that MPTP exposure caused mortality, developmental disorders, locomotor deficits, disruption of circadian rhythm, oxidative stress, and mitochondrial dysfunction in flies. However, KMP supplementation counteracted these toxic effects, improving survival, locomotion, circadian cycle, and restoring antioxidant enzymes and mitochondrial functionality. Therefore, KMP shows promise in mitigating the toxic effects of MPTP and potentially in the treatment of Parkinson's disease.
Article
Oncology
Jing Zhang, Bohao Sun, Jifeng Yang, Zhuo Chen, Zhengzheng Li, Nan Zhang, Hongzhi Li, Luxi Shen
Summary: This study compared the effects of rotenone and MPTP in two commonly used mouse models of chronic PD. The results showed that the MPTP model accurately reproduced the pathological features of PD, while the rotenone model was more suitable for studying mitochondrial dysfunction and Lewy body formation in PD.
MOLECULAR MEDICINE REPORTS
(2022)
Article
Crystallography
Maya Chochkova, Rusi Rusew, Reni Kalfin, Lyubka Tancheva, Maria Lazarova, Hristina Sbirkova-Dimitrova, Andrey Popatanasov, Krasimira Tasheva, Boris Shivachev, Nejc Petek, Martin Sticha
Summary: Parkinson's disease is a common neurodegenerative disorder with severe side effects associated with current treatments. In this study, a new compound, CA(2-Me)-Am, was synthesized and shown to improve memory performance and neuromuscular coordination in an experimental model of Parkinson's disease.
Article
Neurosciences
Mariam D. Oduola-Akande, Ismail O. Ishola, Taiwo G. Olubodun-Obadun, Adeola J. Akande, Olufunmilayo O. Adeyemi
Summary: This study evaluated the effect of glimepiride on MPTP-induced Parkinson's disease in mice. The results showed that glimepiride can ameliorate motor and non-motor deficits caused by MPTP through enhancing antioxidant defense signaling and attenuating neuroinflammatory markers.
NEUROTOXICITY RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Babita Singh, Shivani Pandey, Mohammad Rumman, Shashank Kumar, Prem Prakash Kushwaha, Rajesh Verma, Abbas Ali Mahdi
Summary: The study showed that Bacopa monnieri extract has neuroprotective and neurorescue effects against MPTP-induced degeneration of dopaminergic neurons, potentially slowing down disease progression and delaying neurodegeneration in Parkinson's disease.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Behavioral Sciences
Yongjun Wang, Zhengjia Pu, Yiran Zhang, Zhaohui Du, Zeming Guo, Qunhua Bai
Summary: Parkinson's disease (PD) is a common neurodegenerative disease whose exact cause is unclear, but gut microbial disorders are believed to play a role in its development. This study investigated the effects of exercise training on PD by subjecting a chronic mouse model of the disease to rotarod walking training. The results showed that exercise training improved motor function, increased dopamine content, and promoted the gene expression of important factors in the striatum, indicating potential protection against MPTP-induced damage. Additionally, exercise training promoted recovery from ileal pathology, reduced intestinal inflammation, and significantly altered the composition and structure of the intestinal flora.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Article
Neurosciences
Tsu-Kung Lin, Kai-Jung Lin, Hung-Yu Lin, Kai-Lieh Lin, Min-Yu Lan, Pei-Wen Wang, Tzu-Jou Wang, Feng-Sheng Wang, Po-Chin Tsai, Chia-Wei Liou, Jiin-Haur Chuang
Summary: Parkinson's disease is a common neurodegenerative disorder with no known treatments to slow its progression. Recent studies suggest that anti-diabetic drugs like GLP-1RA may have neuroprotective effects in PD by improving mitochondrial morphology balance and enhancing damaged organelle degradation.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Neurosciences
Lei Wang, Xinghong Wu, Ge Yang, Nan Hu, Zijian Zhao, Lei Zhao, Shengyu Li
Summary: This study investigated the therapeutic effect of cannabidiol (CBD) on Parkinson's disease (PD) mice. The results showed that CBD improved cognitive dysfunction and locomotion in PD mice by inhibiting neuroinflammation and dopaminergic neuron apoptosis.
Article
Biochemistry & Molecular Biology
Navneet Ammal Kaidery, Manuj Ahuja, Sudarshana M. Sharma, Bobby Thomas
Summary: Advancements in healthcare and increased lifespan have improved quality of life but also led to an increased incidence of neurodegenerative diseases. Recent evidence suggests that epigenetic processes can impact pathways related to NDs, with miRNAs being critical for normal neuron functioning. Future research may focus on developing miRNAs as potential biomarkers and therapeutic targets for neuroinflammation in NDs.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Article
Neurosciences
Nam-Shik Kim, Francisca Rojas Ringeling, Ying Zhou, Ha Nam Nguyen, Stephanie J. Temme, Yu-Ting Lin, Stephen Eacker, Valina L. Dawson, Ted M. Dawson, Bo Xiao, Kuei-sen Hsu, Stefan Canzar, Weidong Li, Paul Worley, Kimberly M. Christian, Ki-Jun Yoon, Hongjun Song, Guo-li Ming
Summary: This study investigates the impact of gene dosage imbalance on neuropsychiatric disorders using mouse models. The results suggest that the Cyfip1 gene regulates protein translation of NMDAR and associated complex components at synapses, maintaining normal synaptic functions and behaviors. The findings provide insights into how gene dosage imbalance caused by CNVs may contribute to divergent neuropsychiatric disorders.
BIOLOGICAL PSYCHIATRY
(2022)
Review
Geriatrics & Gerontology
Dmitry M. Hushpulian, Navneet Ammal Kaidery, Manuj Ahuja, Andrey A. Poloznikov, Sudarshana M. Sharma, Irina G. Gazaryan, Bobby Thomas
Summary: The Keap1-Nrf2 signaling axis is a validated and promising target for cellular defense and survival pathways. However, small-molecule displacement activators targeting Keap1 may lead to non-specific effects, releasing not only Nrf2 but also other client proteins from the ubiquitin ligase complex. This lack of specificity could result in off-target effects, unless strategies are employed to ensure specificity for the Kelch domain only in Keap1.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Alexander Popov, Anna Klimovich, Olga Styshova, Alexander Tsybulsky, Dmitry Hushpulian, Andrey Osipyants, Anna Khristichenko, Sergey Kazakov, Manuj Ahuja, Navneet Kaidery, Bobby Thomas, Vladimir Tishkov, Abraham Brown, Irina Gazaryan, Andrey Poloznikov
Summary: Ginsenoside Rh2 enhances the efficacy of doxorubicin treatment in murine models of solid and ascites Ehrlich's adenocarcinoma by suppressing tumor cell adhesion and invasion. Rh2 also reduces the toxicity of doxorubicin towards non-cancerous cells by activating the Nrf2-driven antioxidant program.
Article
Biochemistry & Molecular Biology
Irina N. Gaisina, Dmitry M. Hushpulian, Arsen M. Gaisin, Eliot H. Kazakov, Navneet Ammal Kaidery, Manuj Ahuja, Andrey A. Poloznikov, Irina G. Gazaryan, Gregory R. J. Thatcher, Bobby Thomas
Summary: The newly identified compound has shown strong potential as a stabilizer for Nrf2, with its activity being stronger than the known NMBSA. Its inhibitory action in the commercial fluorescence polarization assay observed only in the millimolar range suggests that it could be a promising candidate for future optimization studies targeting neurodegenerative diseases.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Andrey A. Poloznikov, Sergey V. Nikulin, Dmitry M. Hushpulian, Anna Yu. Khristichenko, Andrey I. Osipyants, Andrey F. Asachenko, Olga V. Shurupova, Svyatoslav S. Savin, Sue H. Lee, Irina N. Gaisina, Gregory R. J. Thatcher, Anthony Narciso, Eric P. Chang, Sergey V. Kazakov, Nancy Krucher, Vladimir I. Tishkov, Bobby Thomas, Irina G. Gazaryan
Summary: This study evaluated the differences in action of commercially available 2-oxoglutarate mimetics and branched-tail oxyquinoline inhibitors of hypoxia-inducible factor prolyl hydroxylase (HIF PHD). Novel oxyquinoline inhibitors were identified to be more active than existing ones and showed opposite effects on certain signaling pathways.
Article
Biochemistry & Molecular Biology
Lun Cai, Ali S. Arbab, Tae Jin Lee, Ashok Sharma, Bobby Thomas, Kazuhiko Igarashi, Raghavan Pillai Raju
Summary: The deletion of Bach1 gene improves organ function and survival in sepsis. It enhances antioxidant response, reduces oxidative stress and inflammation, preserves mitochondrial function, and regulates gene expression related to lipid metabolism. Bach1 deficiency also improves liver and lung blood flow in septic mice.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Neurosciences
Laura Scott, Senthilkumar S. Karuppagounder, Stewart Neifert, Bong Gu Kang, Hu Wang, Valina L. Dawson, Ted M. Dawson
Summary: In this study, a transgenic model was generated to examine the impact of Parkin loss on mitochondrial function in PolgAD257A/D257A mice. Surprisingly, no dopaminergic neurodegeneration or nigral-striatal neurobehavioral deficits were observed in these mice. These findings suggest a lack of synergism between Parkin loss and mitochondrial dysfunction in this mouse model of mitochondrial deficits.
JOURNAL OF NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Manuj Ahuja, Navneet Ammal Kaidery, Debashis Dutta, Otis C. Attucks, Eliot H. Kazakov, Irina Gazaryan, Mitsuyo Matsumoto, Kazuhiko Igarashi, Sudarshana M. Sharma, Bobby Thomas
Summary: Parkinson's disease is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons. Although the exact cause is unclear, oxidative stress, mitochondrial dysfunction, neuroinflammation, and disruption of calcium homeostasis have been proposed as contributing factors. While drugs targeting these pathways have shown promise in preclinical models, a more effective therapeutic approach involving the activation of the Nrf2/Bach1 signaling pathway is being explored. This review discusses the potential benefits of simultaneously inhibiting Bach1 and stabilizing Nrf2 for the treatment of Parkinson's disease.
Article
Clinical Neurology
Jaimin Patel, Nikhil Panicker, Valina L. Dawson, Ted M. Dawson
Summary: Parkinson's disease is a prevalent neurodegenerative disease with no disease-modifying therapies currently available. The parkin protein, known for its role in both autosomal recessive and sporadic Parkinson's disease, has shown potential therapeutic targets, particularly in mitochondrial-related functions.
Article
Biochemistry & Molecular Biology
Juan F. Cervilla-Martinez, Juan J. Rodriguez-Gotor, Krzysztof J. Wypijewski, Angela Fontan-Lozano, Tao Wang, Enrique Santamaria, William Fuller, Rebeca Mejias
Summary: Through data-mining of palmitome in the cerebral cortex of PD patients and controls, the study identified 150 proteins with altered palmitoylation, which are predicted to impact cytoskeleton, mitochondrial and fibrinogen functions, as well as cell survival. The research suggests that protein palmitoylation may play a role in the pathophysiology of PD, and comprehensive palmitoyl-proteomics is a powerful approach for exploring novel cellular pathways involved in this neurodegenerative disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Eleftheria Koropouli, Qiang Wang, Rebeca Mejias, Randal Hand, Tao Wang, David D. Ginty, Alex L. Kolodkin
Summary: The secretion of Sema3F inhibits dendritic spine formation by palmitoylation of Nrp2, while the secretion of Sema3A enhances basal dendrite extension by palmitoylation of Nrp1. These findings demonstrate the essential role of palmitoylation in establishing neuronal structure and functional responses to guidance cues.
Article
Biochemistry & Molecular Biology
Dmitry M. Hushpulian, Navneet Ammal Kaidery, Debashis Dutta, Sudarshana M. Sharma, Irina Gazaryan, Bobby Thomas
Summary: Nrf2 is a key regulator of cellular stress response, while Bach1 acts as a feedback regulator. Excessive accumulation of Bach1 interferes with Nrf2 activation, making it crucial to stabilize Nrf2 and inhibit Bach1 for optimal therapeutic benefits. Developing small molecule inhibitors of Bach1 could be a promising neurotherapeutic strategy.
Editorial Material
Physiology
William Fuller, Rebeca Mejias
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Geriatrics & Gerontology
Xiaogang Chu, Kumar Subramani, Bobby Thomas, Alvin V. Terry, Sadanand Fulzele, Raghavan Pillai Raju
Summary: Studies have shown that factors in the blood of young organisms can rejuvenate the old ones. In this study, it was discovered that treating aged mice with plasma-derived factors from young mice can prolong their lives and reduce oxidative stress. The treatment also modulates the Nrf2/Bach1 axis in the antioxidant response pathway, promoting injury resolution.