Editorial Material
Medicine, Research & Experimental
Paul Wuh-Liang Hwu, Karl Kiening, Irina Anselm, David R. Compton, Takeshi Nakajima, Thomas Opladen, Phillip L. Pearl, Agathe Roubertie, Thomas Roujeau, Shin-ichi Muramatsu
Summary: This commentary provides an overview of the putamen as an established target site for gene therapy in treating AADC deficiency and Parkinson's disease, showcasing the rationale behind targeting this brain structure based on its neuroanatomy and function in motor control. The efficacy and safety of intraputaminal gene therapy in restoring dopamine synthesis by using low doses of adeno-associated viral vector serotype 2 to deliver the hAADC gene are well tolerated, leading to sustained improvements in motor and nonmotor symptoms of AADC deficiency and improved uptake and conversion of exogenous L-DOPA into dopamine in Parkinson's patients.
EMBO MOLECULAR MEDICINE
(2021)
Article
Endocrinology & Metabolism
Nastassja Himmelreich, Riccardo Montioli, Sven F. Garbade, Jeffrey Kopesky, Sarah H. Elsea, Carla Carducci, Carla B. Voltattorni, Nenad Blau
Summary: The research aims to identify pathogenic DDC variants in AADC deficiency, classify and curate variants of unknown significance, and improve the diagnostic accuracy of genetic testing for this condition. By combining in silico variant interpretation tools, structural 3D modeling, and comparative analysis, the current interpretation recommendations for DDC variants have been enhanced.
MOLECULAR GENETICS AND METABOLISM
(2022)
Article
Chemistry, Analytical
Chia-Wen Chang, Yu-Hsuan Lin, Cheng-Han Tsai, Sivasankar Kulandaivel, Yi-Chun Yeh
Summary: A novel heat-stable enzyme was developed for a protein-and cell-based biosensor, enabling the detection of L-DOPA for the first time. The detection of L-DOPA was achieved through a red fluorescent signal within 30 minutes. Furthermore, a sequential analysis method using dual-fluorescent signals was developed for the sensitive detection of dopamine and L-DOPA coexistence, allowing for monitoring of the therapy for Parkinson's disease patients treated with L-DOPA.
ANALYTICA CHIMICA ACTA
(2022)
Article
Biochemistry & Molecular Biology
Sihan Lin, Kai Wang, Bingbing Yang, Bo Li, Xiuli Shen, Zhiqiang Du
Summary: The expression patterns of Pc-dar were investigated after bacterial challenge, and it was found to be related to antibacterial innate immunity. Knocking down Pc-ddc resulted in upregulation of Pc-dar expression and inhibited upregulation of endogenous Pc-DDC enzymatic activities after bacterial stimulation. Melanization in crayfish hemolymph was downregulated after bacterial challenge, and Toll signaling pathway and ROS-related genes were activated in response to bacterial stimulation when Pc-ddc was knocked down.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biotechnology & Applied Microbiology
Yingying Wang, Xueman Chen, Qiaoyu Chen, Ning Zhou, Xin Wang, Alei Zhang, Kequan Chen, Pingkai Ouyang
Summary: This study proposes a one-pot method for the production of 5-HT from L-Trp via two enzyme cascades. A chassis cell capable of converting L-Trp to 5-HTP was constructed by expressing tryptophan hydroxylase from Schistosoma mansoni (SmTPH) and an artificial endogenous tetrahydrobiopterin (BH4) module. Then, dopa decarboxylase from Harminia axyridis (HaDDC) was used for the specific catalysis of 5-HTP to 5-HT. The constructed cell factory, E. coli BL21(DE3)Delta tnaA/BH4/HaDDC-SmTPH, achieved the highest 5-HT concentration of 414.5 +/- 1.6 mg/L (conversion rate of 25.9 mol%) under optimal conditions (substrate concentration of 2 g/L, induced temperature of 25 degrees C, IPTG concentration of 0.5 mM, catalysis temperature of 30 degrees C, catalysis time of 72 h).
MICROBIAL CELL FACTORIES
(2022)
Article
Engineering, Chemical
Siyuan Gao, Yuanke Guo, Chen Ma, Ding Ma, Kequan Chen, Pingkai Ouyang, Xin Wang
Summary: In this study, dopamine was efficiently synthesized using heterologous expression of dopa decarboxylase from Harmonia axyridis in Escherichia coli. The purified dopa decarboxylase was characterized and its optimal conditions for activity were determined. The feasibility of producing dopamine from L-dopa was evaluated and a fed-batch process was developed. The production of dopamine reached a high titer, yield, and productivity under anaerobic conditions.
CHINESE JOURNAL OF CHEMICAL ENGINEERING
(2022)
Article
Biochemistry & Molecular Biology
Vladimir M. Pogorelov, Michael L. Martini, Jian Jin, William C. Wetsel, Marc G. Caron
Summary: L-DOPA is the main treatment for Parkinson's disease, but it can lead to dyskinesia over time. In this study, dopamine-depleted dopamine-transporter KO (DDD) mice were used as an acute PD model to screen novel compounds for anti-parkinsonian and L-DOPA-induced dyskinesia. The researchers found that oral stereotypies could be used as an index for LID in DDD mice.
Article
Cell Biology
George Mpekoulis, Katerina I. Kalliampakou, Raphaela S. Milona, Despoina Lagou, Anastasios Ioannidis, Edison Jahaj, Christos T. Chasapis, Dionysis Kefallinos, Ioannis Karakasiliotis, Anastasia Kotanidou, Stylianos Chatzipanagiotou, Dido Vassilacopoulou, Alice G. Vassiliou, Emmanouil Angelakis, Niki Vassilaki
Summary: SARS-CoV-2 infection is associated with the expression of the dopamine biosynthetic enzyme L-Dopa decarboxylase (DDC). The expression of DDC is negatively correlated with SARS-CoV-2 RNA levels in mild/no symptom COVID-19 patients, but significantly reduced in severe/critical cases, suggesting its potential as a marker of COVID-19 severity.
Article
Biotechnology & Applied Microbiology
Yi Yan, Yajun Bai, Xiaohui Zheng, Yujie Cai
Summary: Hydroxytyrosol (HT), a polyphenolic molecule, is highly valued and used in various industries. Researchers have modified Escherichia coli to enhance the expression of key enzymes and compared different DODC enzymes for efficient HT production. The results showed that the DODC enzyme from Homo sapiens is superior.
ENZYME AND MICROBIAL TECHNOLOGY
(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.
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)
Article
Neurosciences
Keita Sugiyama, Mahomi Kuroiwa, Takahide Shuto, Yoshinori N. Ohnishi, Yukie Kawahara, Yuta Miyamoto, Takaichi Fukuda, Akinori Nishi
Summary: The striatum, the main structure of the basal ganglia, is subdivided into seven subregions with distinct roles in motor and emotional functions. Dopamine D1 receptor signaling is region-specifically regulated in the striatum, with aberrant activation in the IC associated with L-DOPA-induced dyskinesia. Future research focusing on D1 receptor signaling in the IC may lead to novel therapeutics for LID.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Riccardo Viaro, Francesco Longo, Fabrizio Vincenzi, Katia Varani, Michele Morari
Summary: Previous studies have demonstrated that L-DOPA can enhance dopamine release through SCH23390-sensitive D1 receptors and potentially promote dopamine efflux via conversion to dopamine and reversal of the DA transporter.
Article
Genetics & Heredity
Gabriel Civallero, Francyne Kubaski, Danilo Pereira, Gabriel Rubensam, Zackary M. Herbst, Camilo Silva, Franciele B. Trapp, Edina Poletto, Larissa Faqueti, Gabrielle Iop, Juliano Soares, Vanessa van der Linden, Helio van der Linden, Charles M. Lourenco, Roberto Giugliani
Summary: This study developed an analytical method for determining AADC activity and evaluated its ability to confirm AADC deficiency in potential patients in Brazil. The results showed clear discrimination between confirmed AADC deficient patients and healthy controls.
MOLECULAR GENETICS AND METABOLISM REPORTS
(2022)
Article
Genetics & Heredity
Gabriel Civallero, Francyne Kubaski, Danilo Pereira, Gabriel Rubensam, Zackary M. Herbst, Camilo Silva, Franciele B. Trapp, Edina Poletto, Larissa Faqueti, Gabrielle Iop, Juliano Soares, Vanessa van der Linden, Helio van der Linden, Charles M. Lourenco, Roberto Giugliani
Summary: The study aimed to develop a method for determining AADC activity and evaluate its capacity to confirm AADC deficiency in potential patients in Brazil. The results showed clear discrimination between confirmed AADC deficient patients and healthy controls, indicating the method's effectiveness.
MOLECULAR GENETICS AND METABOLISM REPORTS
(2022)
Article
Cell Biology
Vanesa Nieto-Estevez, Cagla Defterali, Carlos Vicario
Summary: This study found that, under in vitro culture conditions, BDNF promotes the morphological differentiation of developing olfactory bulb interneurons and increases the size of synaptic boutons.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2022)
Article
Neurosciences
Isabel Espadas, Oscar Ortiz, Patricia Garcia-Sanz, Adrian Sanz-Magro, Samuel Alberquilla, Oscar Solis, Jose Maria Delgado-Garcia, Agnes Gruart, Rosario Moratalla
Summary: The genetic inactivation of D2R impairs spatial memory, associative learning, and classical conditioning of eyelid responses, as well as reduces activity-dependent synaptic plasticity in the hippocampal CA1-CA3 synapse. These findings demonstrate the key role of D2R in regulating hippocampal plasticity changes and affecting the acquisition and consolidation of spatial and associative forms of memory.
Review
Clinical Neurology
Patricia Garcia-Sanz, Johannes M.F.G. Aerts, Rosario Moratalla
Summary: Parkinson's disease is a progressive neurodegenerative disease associated with dopaminergic neuron loss and alpha-synuclein. The disease develops from interactions between multiple factors, with mutations in the GBA1 gene being a major genetic risk factor. Cholesterol plays a role in PD pathology, particularly in relation to disturbed cellular cholesterol metabolism.
MOVEMENT DISORDERS
(2021)
Article
Cell & Tissue Engineering
Benjamin Schmid, Bjorn Holst, Christian Clausen, Lamiaa Bahnassawy, Peter Reinhardt, Margot H. M. Bakker, Eva Diaz-Guerra, Carlos Vicario, Pamela Martino-Adami, Michaela Thoenes, Alfredo Ramirez, Klaus Flissbach, Clara Grezella, Oliver Bruestle, Michael Peitz, Andreas Ebneth, Alfredo Cabrera-Socorro
Summary: The APOE genotype is the strongest genetic risk factor for AD, and the low homology between mouse and human APOE is a concerning issue in current preclinical models. The ADAPTED project aims to generate in vitro models that better reflect human APOE biology.
STEM CELL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Eddie Grinman, Yoshihisa Nakahata, Yosef Avchalumov, Isabel Espadas, Supriya Swarnkar, Ryohei Yasuda, Sathyanarayanan Puthanveettil
Summary: This study identified a long noncoding RNA named ADEPTR, which is up-regulated and synaptically transported in a cAMP/PKA-dependent manner in hippocampal neurons, independently of its protein-coding host gene. ADEPTR mediates dendritic localization through molecular motor protein Kif2A and binds to actin-scaffolding regulators ankyrin (AnkB) and spectrin (Sptn1) to regulate synaptic structural plasticity.
Article
Cell & Tissue Engineering
Cagla Defterali, Mireia Moreno-Estelles, Carlos Crespo, Eva Diaz-Guerra, Maria Diaz-Moreno, Eva Vergano-Vera, Vanesa Nieto-Estevez, Anahi Hurtado-Chong, Antonella Consiglio, Helena Mira, Carlos Vicario
Summary: In this study, injected EGFP-labeled retroviral particles in the adult olfactory bulb core of mice revealed that NSCs could generate multipotent neurons and glial cells. These newly generated neurons were able to establish synaptic contacts and be integrated into the olfactory bulb circuits.
Article
Endocrinology & Metabolism
Susana Mellado, Beatriz Moreno-Ruiz, Sara Exposito, Miriam Fernandez, Eduardo D. D. Martin
Summary: This study investigates the relationship between pituitary hormones and parvalbumin (PV) expression in the hippocampus, which plays a crucial role in memory and learning. The results show that prolactin (PRL) treatment increases PRL receptor (PRLR) expression and decreases PV expression in the hippocampus. The study also reveals a linear correlation between the reduction in PV expression and the reduction in the beta 2/3 subunit of GABA(A) receptor (GABA(A)R) expression induced by PRL. These findings provide insight into the mechanisms underlying cognitive function changes in hyperprolactinemia.
NEUROENDOCRINOLOGY
(2022)
Article
Cell Biology
Lingling Li, Cristina Medina-Menendez, Laura Garcia-Corzo, Carmen M. Cordoba-Beldad, Alejandra C. Quiroga, Elena Calleja Barca, Valeriya Zinchuk, Sara Munoz-Lopez, Pilar Rodriguez-Martin, Maria Ciorraga, Ines Colmena, Silvia Fernandez, Carlos Vicario, Silvia K. Nicolis, Veronique Lefebvre, Helena Mira, Aixa Morales
Summary: Research shows that SoxD transcription factors Sox5 and Sox6 are enriched in activated radial glia-like neural stem cells, and deletion of these genes in adult mouse brains affects RGL activation and generation of new neurons. Loss of Sox5 also hinders activation of RGLs driven by neurogenic stimuli.
Article
Biochemistry & Molecular Biology
Idaira Oliva, Shahin A. Saberi, Claudia Rangel-Barajas, Vishakh Iyer, Kendra D. Bunner, Yvonne Y. Lai, Pushkar M. Kulkarni, Sumanta Garai, Ganesh A. Thakur, Jonathon D. Crystal, George Rebec, Andrea G. Hohmann
Summary: Disrupting the protein-protein interaction between nNOS and PSD95 can decrease morphine reward and relapse-like behavior. The PSD95-nNOS inhibitor ZL006 reduces morphine-induced increases in dopamine efflux and attenuates morphine relapse behavior.
Article
Neurosciences
Inmaculada Crespo, Jaime Pignatelli, Veena Kinare, Hector R. Mendez-Gomez, Miriam Esgleas, Maria Jose Roman, Josep M. Canals, Shubha Tole, Carlos Vicario
Summary: This study investigates the impact of misexpression of the Tbr1 transcription factor on mouse neural progenitor cells. The results suggest that Tbr1 misexpression delays or disrupts neuronal migration, specification, and dendrite development, potentially leading to brain malformations.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Cell Biology
Francisco J. Fernandez Acosta, Inma Luque-Molina, Rebeca Vecino, Eva Diaz-Guerra, Cagla Defterali, Jaime Pignatelli, Carlos Vicario
Summary: This study found that neural stem cells in the olfactory bulb of adult mice can generate CalR(+) neurons, and these adult cells exhibit different morphologies when migrating to different layers of the olfactory bulb. The study also revealed that altering the expression of the transcription factor Tbr1 can affect the migration and morphology of these newly generated neurons.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biology
Alejandro Sola-Garcia, Maria Angeles Caliz-Molina, Isabel Espadas, Michael Petr, Concepcion Panadero-Moron, Daniel Gonzalez-Moran, Maria Eugenia Martin-Vazquez, Alvaro Jesus Narbona-Perez, Livia Lopez-Noriega, Guillermo Martinez-Corrales, Raul Lopez-Fernandez-Sobrino, Lina M. Carmona-Marin, Enrique Martinez-Force, Oscar Yanes, Maria Vinaixa, Daniel Lopez-Lopez, Jose Carlos Reyes, Joaquin Dopazo, Franz Martin, Benoit R. Gauthier, Morten Scheibye-Knudsen, Vivian Capilla-Gonzalez, Alejandro Martin-Montalvo
Summary: A multiomic approach reveals that long-term exposure to the Acly inhibitor SB-204990 can modulate molecular mechanisms associated with aging. ATP-citrate lyase has a crucial role in cellular metabolism, integrating the protein, carbohydrate, and lipid metabolism. In vivo studies using untargeted metabolomics, transcriptomics, and proteomics show that SB-204990 regulates energy metabolism, mitochondrial function, mTOR signaling, and folate cycle, and can prevent the development of metabolic abnormalities associated with an unhealthy diet.
COMMUNICATIONS BIOLOGY
(2023)
Article
Geriatrics & Gerontology
Irene Costa-Laparra, Elena Juarez-Escoto, Carlos Vicario, Rosario Moratalla, Patricia Garcia-Sanz
Summary: Alzheimer's disease is characterized by memory loss and the presence of senile plaques and neurofibrillary tangles. This study investigates the impact of APOE ε4 and G206D-PSEN1 on the underlying mechanisms of Alzheimer's disease, including autophagy pathway and mitochondrial dysfunction.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Biology
Raquel Herrero-Labrador, Joaquin Fernandez-Irigoyen, Rebeca Vecino, Candela Gonzalez-Arias, Karina Ausin, Inmaculada Crespo, Francisco Fernandez Acosta, Vanesa Nieto-Estevez, M. Jose Roman, Gertrudis Perea, Ignacio Torres-Aleman, Enrique Santamaria, Carlos Vicario
Summary: By conditional deletion of Igf-I in the nervous system, we found that long-term potentiation was impaired in hippocampal slices. Igf-I1 /1 mice showed spatial memory deficits in the Morris water maze and the sex-dependent differences displayed in Igf-ICtrl/Ctrl mice disappeared in Igf-I1 /1 mice in the open field and rota-rod tests. Brain Igf-I deletion disrupted the granule cell layer of the dentate gyrus and altered the relative expressions of GAD and VGLUT1, affecting inhibitory and excitatory presynaptic terminals. Furthermore, Igf-I deletion affected protein modules involved in receptor trafficking, synaptic proteins, and proteins related to estrogen and androgen metabolism. These findings highlight the crucial role of brain IGF-I in long-term potentiation and its involvement in spatial memory and sexual dimorphic behaviors through the maintenance of granule cell layer structure and stability of synaptic-related protein modules.
LIFE SCIENCE ALLIANCE
(2023)
Article
Neurosciences
Nihal A. Salem, Lawrence Manzano, Michael W. Keist, Olga Ponomareva, Amanda J. Roberts, Marisa Roberto, R. Dayne Mayfield
Summary: This study identified cell-type specific gene expression changes associated with alcohol dependence in the medial prefrontal cortex of mice. The results revealed dysregulated gene co-expression networks and differentially expressed genes in multiple cell types, highlighting the involvement of inhibitory neurons and astrocytes in alcohol dependence. Novel targets for studying molecular mechanisms contributing to alcohol dependence were also identified.
NEUROBIOLOGY OF DISEASE
(2024)
Article
Neurosciences
Laura E. Hawley, Megan Stringer, Abigail J. Deal, Andrew Folz, Charles R. Goodlett, Randall J. Roper
Summary: This study found that the overexpression of DYRK1A protein in Down syndrome mice varies with age, sex, and brain region, and reducing the copy number of Dyrk1a can decrease the expression of DYRK1A. These sex-specific patterns of DYRK1A overexpression may provide mechanistic targets for therapeutic intervention in Down syndrome.
NEUROBIOLOGY OF DISEASE
(2024)