Review
Cell Biology
Destany K. K. Kwon, Mohit Kwatra, Jing Wang, Han Seok Ko
Summary: Levodopa is the most commonly used treatment for Parkinson's disease (PD) but comes with side effects in the advanced stages of the disease. Understanding the pathological mechanisms of levodopa-induced dyskinesia (LID) and finding alternative treatment options are crucial for improving the outcome of PD patients.
Article
Neurosciences
Annalisa Pinna, Pathik Parekh, Micaela Morelli
Summary: This review discusses the role of serotonin 5-HT1A receptors and adenosine A2A receptors in dyskinetic movements induced by chronic levodopa in Parkinson's Disease (PD) patients. Preclinical and clinical studies have shown the interaction between serotonin 5-HT1A receptors and other receptors, such as 5-HT1B receptors and adenosine A2A receptors. The combination of 5-HT1A/1B receptor agonists and A2A receptor antagonists effectively counteracts dyskinetic movements induced by chronic levodopa without impairing motor behavior, suggesting a potential therapeutic approach for PD motor deficits and levodopa-induced dyskinesia.
Article
Biochemistry & Molecular Biology
Tung-Tai Kuo, Yuan-Hao Chen, Vicki Wang, Eagle Yi-Kung Huang, Kuo-Hsing Ma, Nigel H. H. Greig, Jin Jung, Ho- Choi, Lars Olson, Barry J. J. Hoffer, Kuan-Yin Tseng
Summary: This study evaluated the efficacy of PT320 on L-DOPA-induced dyskinetic behaviors and neurochemistry in a progressive Parkinson's disease MitoPark mouse model. The results showed that early administration of PT320 significantly reduced the severity of L-DOPA-induced abnormal involuntary movements, particularly in excessive standing and abnormal paw movements. However, late administration of PT320 did not improve any L-DOPA-induced dyskinesia measurements. Furthermore, early treatment with PT320 increased both tonic and phasic release of dopamine in striatal slices, indicating its potential role in alleviating L-DOPA-induced dyskinesia in Parkinson's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Kathryn Lanza, Christopher Bishop
Summary: Parkinson's Disease (PD) and long-term L-DOPA treatment induce plasticity that contributes to L-DOPA-induced dyskinesia (LID), with the dopamine D3 receptor (D3R) emerging as a promising target in LID management due to its upregulation in LID. D3R undergoes dynamic changes in both PD and LID, and recent genetic and pharmacologic tools have helped clarify its role in LID.
Review
Clinical Neurology
Valtteri Kaasinen, Tero Vahlberg, A. Jon Stoessl, Antonio P. Strafella, Angelo Antonini
Summary: This study conducted a systematic review and meta-analysis on the expression of dopamine receptors in PD, PSP, and MSA, revealing differences in binding values of dopamine receptors among patients with different diseases.
MOVEMENT DISORDERS
(2021)
Article
Pharmacology & Pharmacy
Qian Zhang, XiangTing Chen, FeiFei Chen, SiYuan Wen, ChangQing Zhou
Summary: Compared with levodopa, dopamine agonists (DAs) as initial treatment are associated with lower incidences of motor complications in early Parkinson's disease (PD). There is no strong evidence that a given DA is more potent in lower incidences of motor complications than another. We performed a network meta-analysis of levodopa versus DAs as monotherapy in early PD to assess the risk of motor complications.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Mechelle M. Lewis, Lauren J. Van Scoy, Sol De Jesus, Jonathan G. Hakun, Paul J. Eslinger, Julio Fernandez-Mendoza, Lan Kong, Yang Yang, Bethany L. Snyder, Natalia Loktionova, Sridhar Duvvuri, David L. Gray, Xuemei Huang, Richard B. Mailman
Summary: Current pharmacotherapy has limited efficacy and intolerable side effects in late-stage Parkinson's disease patients. A study was conducted to explore the efficacy of a D-1/5 dopamine agonist in these patients. Caregiver assessment was used as the primary efficacy measure, and the results showed that the D-1/5 agonist had better efficacy compared to levodopa in most patients.
Editorial Material
Plant Sciences
Peng Wang, Erik Limpens, Ruifeng Yao
Summary: A recent study by Shi et al. reveals a transcriptional regulatory network for arbuscular mycorrhizal symbiosis in rice. The study highlights the importance of PHR transcription factors in coordinating the pathways for inorganic phosphate uptake, opening up opportunities for plant breeding to enhance nutrient acquisition.
TRENDS IN PLANT SCIENCE
(2022)
Review
Medical Laboratory Technology
Saad Latif, Muhammad Jahangeer, Dure Maknoon Razia, Mehvish Ashiq, Abdul Ghaffar, Muhammad Akram, Aicha El Allam, Abdelhakim Bouyahya, Larisa Garipova, Mohammad Ali Shariati, Muthu Thiruvengadam, Mohammad Azam Ansari
Summary: This article briefly reviews the synthesis pathway of dopamine in Parkinson's disease, its distribution and receptor family, as well as the compounds formed during the oxidation process. By discussing the role of dopamine and its mechanism in Parkinson's disease, it reveals its dual effects in neurotoxicity and neuroprotection.
CLINICA CHIMICA ACTA
(2021)
Article
Neurosciences
Yong Wang, Lu Yao, Shasha Gao, Gejuan Zhang, Qiongchi Zhang, Wanyuan Liu, Yingqiong Zhou, Yina Sun, Jie Feng, Jian Liu
Summary: The study found that the striatal dopamine D-5 receptor plays an important role in the pathophysiology of levodopa-induced dyskinesia in patients with Parkinson's disease, by regulating the activity of sensorimotor striatum neurons to affect the development of dyskinetic symptoms.
Article
Pharmacology & Pharmacy
Jin Zhang, Xiaobing Wang, Rick E. Bernardi, Jun Ju, Shoupeng Wei, Zhiting Gong
Summary: This study found that activation of AMPA receptors in the lateral habenula can reduce anxiety-like behaviors and increase dopamine and serotonin levels in the basolateral amygdala. Conversely, blocking AMPA receptors in the LHb may induce anxiety-like effects and decrease dopamine and serotonin levels in the BLA.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Jace Jones-Tabah
Summary: Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the deterioration of dopaminergic neurons and motor impairment. Although there is no cure for PD, dopamine replacement therapies like L-DOPA can alleviate motor symptoms. However, non-motor symptoms and the progression of neurodegeneration still lack effective treatments. This review focuses on G protein-coupled receptors (GPCRs) as potential targets for treating PD and discusses various therapeutic strategies.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Clinical Neurology
Valtteri Kaasinen, Sheng Luo, Pablo Martinez-Martin, Christopher G. G. Goetz, Glenn T. T. Stebbins
Summary: This study compared patient and clinician evaluations of levodopa-induced dyskinesia (LID) severity across multiple cultures in patients with Parkinson's disease (PD). The results showed that language and cultural differences influence the subjective perception of LID, which is important to consider in multinational clinical trials on dyskinesia assessment.
MOVEMENT DISORDERS
(2023)
Article
Neurosciences
Ivan Castela, Raquel Casado-Polanco, Yaiza Van-Waes Rubio, Joaquim Alves da Silva, Raquel Marquez, Beatriz Pro, Rosario Moratalla, Peter Redgrave, Rui M. Costa, Jose Obeso, Ledia F. Hernandez
Summary: This study used a rodent model to investigate the striatal outflow circuitry responsible for L-DOPA-induced dyskinesias (LIDs) in Parkinson's disease (PD). The activation of the indirect pathway was found to effectively suppress LIDs, highlighting the importance of maintaining an equilibrium in the activity of both striatal pathways for normal movement. These findings provide insights into the intrinsic mechanisms and potential therapeutic targets for suppressing LIDs in PD patients.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Automation & Control Systems
Florian Dorfler, Jeremy Coulson, Ivan Markovsky
Summary: In this article, the connections between sequential system identification and control for linear time-invariant systems, known as indirect data-driven control, and a direct data-driven control approach are discussed. The direct approach seeks an optimal decision that is compatible with recorded data assembled in a Hankel matrix and robustified through appropriate regularizations. Two methods from subspace identification and control, subspace predictive control and low-rank approximation, are used to illustrate the results. It is concluded that direct and regularized data-driven control can be derived as convex relaxation of the indirect approach.
IEEE TRANSACTIONS ON AUTOMATIC CONTROL
(2023)
Article
Cell Biology
Myoung Seok Ko, Ji Young Yun, In-Jeoung Baek, Jung Eun Jang, Jung Jin Hwang, Seung Eun Lee, Seung-Ho Heo, David A. Bader, Chul-Ho Lee, Jaeseok Han, Jong-Seok Moon, Jae Man Lee, Eun-Gyoung Hong, In-Kyu Lee, Seong Who Kim, Joong Yeol Park, Sean M. Hartig, Un Jung Kang, David D. Moore, Eun Hee Koh, Ki-up Lee
Summary: This study revealed the role of a specific gene, pink1, in mitochondrial autophagy, where its deficiency induces dysfunction in brown adipose tissue and obesity. Surprisingly, the induction of NLRP3 did not lead to canonical inflammasome activity, but instead caused brown adipocyte precursors to differentiate into white-like adipocytes. These findings suggest a new mitochondria-NLRP3 pathway that contributes to BAT dysfunction and provide potential therapeutic targets for obesity-related metabolic diseases.
Article
Clinical Neurology
Christina D. Orru, Thong C. Ma, Andrew G. Hughson, Bradley R. Groveman, Ankit Srivastava, Douglas Galasko, Rachel Angers, Patrick Downey, Karen Crawford, Samantha J. Hutten, Un Jung Kang, Byron Caughey
Summary: The study shows that an improved assay for diagnosing Parkinson's disease dramatically reduces the diagnosis time while maintaining high performance standards. Positive signals were found in 97% of Parkinson's disease cases compared to only 13% of healthy controls, with weak correlations between assay parameters and clinical measures observed. The assay's efficiency in diagnosing Parkinson's disease is supported by these findings.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Editorial Material
Neurosciences
Bastiaan R. Bloem, Claudia Trenkwalder, Alvaro Sanchez-Ferro, Lorraine V. Kalia, Roy Alcalay, Han-Lin Chiang, Un Jung Kang, Christopher Goetz, Patrik Brundin, Stella M. Papa
Summary: Despite concerns raised by people with Parkinson's disease (PD) and their physicians regarding the efficacy and safety of COVID-19 vaccines in the specific context of PD and its treatment, current literature and experience with widespread vaccination suggest that COVID-19 vaccination with approved vaccines is recommended for PD patients, unless there is a specific contraindication.
JOURNAL OF PARKINSONS DISEASE
(2021)
Article
Clinical Neurology
Suman Dutta, Simon Hornung, Adira Kruayatidee, Katherine N. Maina, Irish del Rosario, Kimberly C. Paul, Darice Y. Wong, Aline Duarte Folle, Daniela Markovic, Jose-Alberto Palma, Geidy E. Serrano, Charles H. Adler, Susan L. Perlman, Wayne W. Poon, Un Jung Kang, Roy N. Alcalay, Miriam Sklerov, Karen H. Gylys, Horacio Kaufmann, Brent L. Fogel, Jeff M. Bronstein, Beate Ritz, Gal Bitan
Summary: The study found that measuring α-syn in exosomes from blood can effectively distinguish between patients with PD and MSA with high sensitivity and specificity. A multinomial logistic model combining α-syn concentration, exosome concentration, and a ratio between α-syn concentrations in specific exosomes showed promising results in separating PD from MSA.
ACTA NEUROPATHOLOGICA
(2021)
Correction
Clinical Neurology
Suman Dutta, Simon Hornung, Adira Kruayatidee, Katherine N. Maina, Irish del Rosario, Kimberly C. Paul, Darice Y. Wong, Aline Duarte Folle, Daniela Markovic, Jose-Alberto Palma, Geidy E. Serrano, Charles H. Adler, Susan L. Perlman, Wayne W. Poon, Un Jung Kang, Roy N. Alcalay, Miriam Sklerov, Karen H. Gylys, Horacio Kaufmann, Brent L. Fogel, Jeff M. Bronstein, Beate Ritz, Gal Bitan
Summary: A correction to the paper has been published.
ACTA NEUROPATHOLOGICA
(2021)
Review
Biochemistry & Molecular Biology
Eleanor H. Simpson, Eduardo F. Gallo, Peter D. Balsam, Jonathan A. Javitch, Christoph Kellendonk
Summary: Research suggests that the etiology of schizophrenia involves overstimulation of dopamine receptors, particularly the D2 receptors. Animal models have shown that alterations in D2 receptor levels can affect the manifestation of schizophrenia symptoms, especially in terms of striatal circuit function and motivated behavior.
MOLECULAR PSYCHIATRY
(2022)
Letter
Clinical Neurology
Luis Concha-Marambio, Carly M. Farris, Bret Holguin, Yihua Ma, John Seibyl, Marco J. Russo, Un J. Kang, Samantha J. Hutten, Kalpana Merchant, Mohammad Shahnawaz, Claudio Soto
MOVEMENT DISORDERS
(2021)
Article
Biochemistry & Molecular Biology
Eduardo F. Gallo, Julia Greenwald, Jenna Yeisley, Eric Teboul, Kelly M. Martyniuk, Joseph M. Villarin, Yulong Li, Jonathan A. Javitch, Peter D. Balsam, Christoph Kellendonk
Summary: Cholinergic interneurons in the striatum respond to salient stimuli with a pause in activity, which is regulated by dopamine D2 receptors. Upregulation of D2Rs in these neurons leads to a prolonged pause in activity and an enhanced decrease in acetylcholine levels during behavior, resulting in a deficit in learning inhibitory responses. This study highlights the important role of CIN D2Rs in modulating responses to salient stimuli and their impact on inhibitory learning.
MOLECULAR PSYCHIATRY
(2022)
Article
Neurosciences
Laura J. Benoit, Emma S. Holt, Lorenzo Posani, Stefano Fusi, Alexander Z. Harris, Sarah Canetta, Christoph Kellendonk
Summary: The study reveals that inhibiting the thalamus during adolescence can lead to long-lasting changes in prefrontal cortex function and behavior, highlighting the importance of thalamic activity in the maturation of prefrontal circuits. These findings provide insights into the potential mechanisms underlying neurodevelopmental disorders.
NATURE NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Marine Laporte, Kwang Chi, Laura Caudal, Na Zhao, Yvonne Schwarz, Marta Rolland, Jose Martinez-Hernandez, Magalie Martineau, Christine Chatellard, Eric Denarier, Vincent Mercier, Florent Lemaitre, Beatrice Blot, Eve Moutaux, Maxime Cazorla, David J. Perrais, Fabien Lante, Dieter Bruns, Sandrine Fraboulet, Fiona Hemming, Frank Kirchhoff, Remy Sadoul
Summary: This study shows that Alix is involved in regulating bulk endocytosis at synapses during high frequency stimulation, and impairment of this process due to the lack of Alix results in abnormal synaptic recovery and plasticity.
Article
Biology
Kelly M. Martyniuk, Arturo Torres-Herraez, Daniel C. Lowes, Marcelo Rubinstein, Marie A. Labouesse, Christoph Kellendonk
Summary: In the striatum, the activity of acetylcholine neurons is regulated by dopamine release, and this regulation is mediated by dopamine D2 receptors. Through experiments on mice, it was found that D2 receptors affect the duration of acetylcholine level changes and regulate the temporal correlation between the two signals. These results suggest an important role of D2 receptors in motivation to initiate actions.
Article
Neurosciences
Giulietta Maria Riboldi, Marco J. Russo, Ling Pan, Kristen Watkins, Un Jung Kang
Summary: Non-motor symptoms like dysautonomia and REM sleep behavior disorder in Parkinson's disease may indicate different types of the disease. Through analysis of data from newly diagnosed Parkinson's patients, it was found that dysautonomia symptoms can predict disease progression more accurately.
NPJ PARKINSONS DISEASE
(2022)
Article
Biology
Sarah E. Canetta, Emma S. Holt, Laura J. Benoit, Eric Teboul, Gabriella M. Sahyoun, R. Todd Ogden, Alexander Z. Harris, Christoph Kellendonk
Summary: In their study, Hubel and Wiesel identified sensitive periods where experience can have long-lasting effects on adult visual cortical functioning and behavior through changes in neuronal activity. They investigated whether similar sensitive periods exist for non-sensory cortices and found that inhibition of prefrontal parvalbumin (PV)-expressing interneurons during the juvenile and adolescent period leads to persistent impairments in adult prefrontal circuit connectivity, in vivo network function, and behavioral flexibility, which can be reversed by targeted activation of PV interneurons in adulthood.
Correction
Neurosciences
Giulietta Maria Riboldi, Marco J. Russo, Ling Pan, Kristen Watkins, Un Jung Kang
NPJ PARKINSONS DISEASE
(2023)
Article
Clinical Neurology
Yong Hu, Thong C. Ma, Stephanie L. Alberico, Yunmin Ding, Lingjing Jin, Un Jung Kang
Summary: This study aimed to determine whether direct modulation of SNr GABAergic neurons and SNr projections to the PPN can regulate PD symptoms and levodopa-induced dyskinesia (LID). The results showed that suppressing SNr neuron activity improved akinesia, while increasing SNr neuronal activity significantly reduced LID. The projections from SNr to PPN likely mediate the antidyskinetic effect of increasing SNr neuronal activity.
MOVEMENT DISORDERS
(2023)