Article
Biochemistry & Molecular Biology
Lakkoji Satish, Santanu Santra, Mikhail Tsurkan, Carsten Werner, Madhurima Jana, Harekrushna Sahoo
Summary: GDNF shows therapeutic potential in treating neurodegenerative diseases, and its activity relies heavily on interactions with sulfated glycans. Experimental and theoretical studies demonstrate that sulfated GAG molecules can strongly bind with GDNF peptide and induce an alpha-helical structure in the peptide to some extent.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Neurosciences
Ella A. Kasanga, Yoonhee Han, Walter Navarrete, Robert McManus, Marla K. Shifflet, Caleb Parry, Arturo Barahona, Fredric P. Manfredsson, Vicki A. Nejtek, Jason R. Richardson, Michael F. Salvatore
Summary: Although GDNF has shown efficacy in alleviating parkinsonian signs in PD patients in preclinical and early clinical studies, later trials did not meet primary endpoints, indicating a need for further investigation. The expression of GFR-alpha 1 and RET, two cognate receptors for GDNF, differed between the striatum and substantia nigra, and their differential expression in nigrostriatal neurons correlated with TH cell loss, suggesting that targeting loss of GDNF receptors may enhance therapeutic efficacy against nigrostriatal neuron loss in PD.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Genetics & Heredity
Himasadat Zaker, Mazdak Razi, Alireza Mahmoudian, Farhad Soltanalinejad
Summary: The study shows that testosterone stimulates the production of Gdnf in Sertoli cells, while Gdnf amplifies its receptor expression to affect the self-renewal of spermatogonial stem cells and spermatogenesis. Both testosterone and Gdnf can up-regulate the expression of Gdnf receptors at different concentrations.
Review
Cell Biology
Jian Liu, Lars C. Pedersen
Summary: This article summarizes the recent progress in substrate specificity studies of different 3-O-sulfotransferase isoforms and introduces a newly developed method for analyzing the level of 3-O-sulfated heparan sulfate using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Sandro Sonnino
Summary: GM1 is a main ganglioside in the nervous system and plays a crucial role in the neurotrophic and neuroprotective functions of neurons. It is involved in various processes essential for the proper functioning of neuronal cells, including the activity of receptors controlling differentiation, survival, and mitochondrial activity. GM1 deficiency in the substantia nigra may contribute to the neurodegeneration observed in Parkinson's disease.
Article
Oncology
Lin Liu, Liqiong Zhao, Jie Zhang, Guoxiang Song, Carol L. Shields, Ruihua Wei
Summary: The study suggests that perineural invasion (PNI) may contribute to the recurrence of lacrimal adenoid cystic carcinoma (LACC). Patients with concurrent expression of GFR alpha-1 and RET proteins may have a higher risk of PNI and recurrence.
CANCER BIOLOGY & MEDICINE
(2021)
Article
Chemistry, Multidisciplinary
Imlirenla Pongener, Conor O'Shea, Hannah Wootton, Michael Watkinson, Gavin J. Miller
Summary: This review focuses on the chemical approaches and methodology improvements for the synthesis of heparin and heparan sulfate since 2015, including advances in accessing the pentasaccharide anticoagulant and targets for heparan sulfate synthesis. It also discusses key building block synthesis, oligosaccharide construction, chemical sulfation techniques, and technological improvements to traditional solution-phase synthesis approaches.
Article
Neurosciences
Carl G. Gottschalk, Malabendu Jana, Avik Roy, Dhruv R. Patel, Kalipada Pahan
Summary: Research suggests that gemfibrozil can protect dopaminergic neurons in an animal model of PD, increase neurotransmitters in the striatum, and improve locomotor activities.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Jesper Bergwik, Amanda Kristiansson, Jorgen Larsson, Simon Ekstrom, Bo Akerstrom, Maria Allhorn
Summary: A1M can bind to heparin and HS, and can be purified from human plasma using heparin affinity chromatography and size exclusion chromatography. The binding strength is inversely proportional to salt concentration and directly proportional to the sulfation degree of heparin and HS.
Article
Developmental Biology
Ana Paula De Vincenti, Fernando C. Alsina, Facundo Ferrero Restelli, Hakan Hedman, Fernanda Ledda, Gustavo Paratcha
Summary: Negative feedback loops, including Lrig1 and Lrig3, regulate Ret signaling in mouse DRG neurons to control axonal growth and sensory sensitivity. These Lrig proteins act redundantly to ensure proper cutaneous innervation and cold behavioral responses, potentially through increased expression of the cold-responsive channel TrpA1.
Article
Biochemistry & Molecular Biology
Angela Boyce, Gary Walsh
Summary: Heparinases are enzymes that selectively cleave heparin and heparan sulfate chains, with potential therapeutic applications in cancer treatment, inhibition of neovascularization, and other biological processes. Their industrial and clinical significance has been underscored by their ability to produce low molecular weight heparin and neutralize heparin in blood.
Review
Biochemistry & Molecular Biology
Mingjia Yu, Tianji Zhang, Wei Zhang, Qianyun Sun, Hongmei Li, Jin-ping Li
Summary: The infectious disease caused by SARS-CoV-2 has become a major threat with high mortality rates and rapid spread, leading to over 70 million infections and 1.6 million deaths. New strategies are urgently needed for treatment due to the lack of effective therapeutics or widely available vaccines. The use of heparin/HS and their mimetics may serve as potential drugs by competing with cell surface HS to prevent viral adhesion and modulate inflammatory reactions, highlighting the importance of understanding coronavirus invasion mechanisms and HS-protein interactions for potential treatment avenues.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Cell Biology
Lucas B. Doretto, Arno J. Butzge, Rafael T. Nakajima, Emanuel R. M. Martinez, Beatriz Marques de Souza, Maira da Silva Rodrigues, Ivana F. Rosa, Juliana M. B. Ricci, Aldo Tovo-Neto, Daniel F. Costa, Guilherme Malafaia, Changwei Shao, Rafael H. Nobrega
Summary: In this study, the roles of the Gdnf-Gfr alpha 1 signaling pathway in zebrafish testes were investigated using in vivo, in silico, and ex vivo approaches. The findings showed that Gdnf promotes the creation of new available niches and inhibits late spermatogonial differentiation in zebrafish.
Article
Biochemistry & Molecular Biology
Samuel G. Holmes, Umesh R. Desai
Summary: Although molecular docking remains challenging for glycosaminoglycans (GAGs) due to their flexibility and anionic character, using a semi-rigid docking protocol can better reproduce the native topology of heparin/heparan sulfate (Hp/HS). Rigid and semi-rigid protocols are more accurate in predicting longer chain poses, while the semi-rigid approach is better for 2-4-mer poses. The new semi-rigid protocol, combined with a new computational parameter, shows promising potential for high-throughput screening of GAG sequences and identifying drug targets and drug-like Hp/HS sequences.
Article
Biotechnology & Applied Microbiology
Bryan E. Thacker, Kristen J. Thorne, Colin Cartwright, Jeeyoung Park, Kimberly Glass, Annie Chea, Benjamin P. Kellman, Nathan E. Lewis, Zhenping Wang, Anna Di Nardo, Susan T. Sharfstein, Walter Jeske, Jeanine Walenga, John Hogwood, Elaine Gray, Barbara Mulloy, Jeffrey D. Esko, Charles A. Glass
Summary: Heparin, an essential anticoagulant, is currently sourced from vulnerable animal populations. This study demonstrates the feasibility of producing high anticoagulant potency heparin sulfate through genome engineering in cell culture, providing a potential alternative to animal sources.
METABOLIC ENGINEERING
(2022)
Article
Substance Abuse
Maryna Koskela, T. Petteri Piepponen, Jaan-Olle Andressoo, Vootele Voikar, Mikko Airavaara
Summary: This study developed a model to investigate alcohol-seeking behavior in group-housed female mice after withdrawal. The results suggest that long-term conditioning with alcohol reward can lead to cue-induced alcohol-seeking behavior. The number of nosepokes in the conditioned corner may be a determining factor for alcohol-seeking after withdrawal.
ALCOHOL AND ALCOHOLISM
(2022)
Article
Biochemistry & Molecular Biology
Elisa Rahikkala, Lea Urpa, Bishwa Ghimire, Hande Topa, Mitja Kurki, Maryna Koskela, Mikko Airavaara, Eija Hamalainen, Katri Pylkas, Jarmo Korkko, Helena Savolainen, Anu Suoranta, Aida Bertoli-Avella, Arndt Rolfs, Pirkko Mattila, Mark Daly, Aarno Palotie, Olli Pietilainen, Jukka Moilanen, Outi Kuismin
Summary: Biallelic loss-of-function variants in the SMG9 gene cause heart and brain malformation syndrome. This study identified a novel pathogenic variant in SMG9 and demonstrated its impact on gene expression, although it had minimal effect on NMD.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Engineering, Biomedical
Samuel Rantataro, Ilmari Parkkinen, Ishan Pande, Andrii Domanskyi, Mikko Airavaara, Emilia Peltola, Tomi Laurila
Summary: Vertically aligned carbon nanofibers (VACNFs) have the potential to detect neurotransmitters, but their high rigidity may lead to mechanical mismatch with brain tissue. By adjusting fiber length and distance, the mechanical biocompatibility of VACNFs can be improved, reducing the formation of glial scars and impacting cell morphology.
ACTA BIOMATERIALIA
(2022)
Article
Chemistry, Medicinal
Dale W. Prebble, Safak Er, Irena Hlushchuk, Andrii Domanskyi, Mikko Airavaara, Merrick G. Ekins, George D. Mellick, Anthony R. Carroll
Summary: This article introduces the potential of preventing the aggregation of certain amyloid proteins to slow down the progression of diseases like Alzheimer's, Parkinson's, and type 2 diabetes mellitus. Through a high-throughput screen of 300 Australian marine invertebrate extracts, the extract of the marine sponge Thorectandra sp. 4408 showed binding activity to the Parkinson's disease-associated protein, alpha-synuclein. The active component isolated from this extract was identified as the known plant growth promoter asterubine (1), which shares structural similarities with amyloid beta aggregation inhibitors tramiprosate (homotaurine) and ALZ-801. This study reports the isolation, NMR data acquired in DMSO, and alpha-synuclein binding activity of asterubine (1).
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biology
Kristen Kurtzeborn, Hyuk Nam Kwon, Vladislav Iaroshenko, Imrul Faisal, Martin Ambroz, Xing Jin, Talha Qureshi, Jussi Kupari, Anneliis Ihermann-Hella, Juho Vaananen, Henna Tyynismaa, Iva Bousova, Sunghyouk Park, Satu Kuure
Summary: Through RNA sequencing and tissue-specific MAPK/ERK inactivation experiments, we found that MAPK/ERK signaling maintains ureteric bud tip cells, potentially playing a regulatory role in collecting duct progenitors. Additionally, we provide new mechanistic insights on how MAPK/ERK signaling regulates progenitor maintenance through its effects on chromatin accessibility and energy metabolism.
Article
Developmental Biology
Hyuk Nam Kwon, Kristen Kurtzeborn, Vladislav Iaroshenko, Xing Jin, Abigail Loh, Nathalie Escande-Beillard, Bruno Reversade, Sunghyouk Park, Satu Kuure
Summary: Nephron endowment plays a crucial role in adult renal health, and defects in the molecular regulation of nephron progenitors can lead to reduced nephron mass. This study characterized the metabolic consequences of MAPK/ERK deficiency and identified pyruvate and proline as important factors in nephron progenitor maintenance.
Article
Developmental Biology
Abhishek Sharma, Marco Meer, Arvydas Dapkunas, Anneliis Ihermann-Hella, Satu Kuure, Seppo J. Vainio, Dagmar Iber, Florence Naillat
Summary: FGF8 plays a crucial role in the condensation of nephron progenitor cells towards the epithelial ureteric buds in the kidney development, by exerting a strong chemokinetic effect.
Review
Cell Biology
Johanna Uusimaa, Johannes Kettunen, Teppo Varilo, Irma Jarvela, Jukka Kallijarvi, Helena Kaariainen, Minna Laine, Risto Lapatto, Paivi Myllynen, Harri Niinikoski, Elisa Rahikkala, Anu Suomalainen, Ritva Tikkanen, Henna Tyynismaa, Paivi Vieira, Tomas Zarybnicky, Petra Sipila, Satu Kuure, Reetta Hinttala
Summary: Isolated populations provide valuable resources for the study of rare monogenic diseases and their genetic variants. Finnish disease heritage (FDH) is an example of a group of hereditary monogenic disorders caused by enriched single major variants in the population due to past genetic drift events. This Review summarizes the current status of FDH, including recently discovered disorders and other related diseases, and discusses the use of population-based studies and big data for identifying new genotype-phenotype associations.
DISEASE MODELS & MECHANISMS
(2022)
Review
Biochemistry & Molecular Biology
Safak Er, Mikko Airavaara
Summary: Alpha-synuclein is a significant component of Lewy bodies and the main histopathology of synucleinopathies. GDNF and CDNF are two neurotrophic factors that have shown potential in treating Parkinson's disease by modulating abnormal alpha-synuclein accumulation.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Article
Neurosciences
Vassilis Stratoulias, Rocio Ruiz, Shigeaki Kanatani, Ahmed M. Osman, Lily Keane, Jose A. Armengol, Antonio Rodriguez-Moreno, Adriana-Natalia Murgoci, Irene Garcia-Dominguez, Isabel Alonso-Bellido, Fernando Gonzalez Ibanez, Katherine Picard, Guillermo Vazquez-Cabrera, Mercedes Posada-Perez, Nathalie Vernoux, Dario Tejera, Kathleen Grabert, Mathilde Cheray, Patricia Gonzalez-Rodriguez, Eva M. Perez-Villegas, Irene Martinez-Gallego, Alejandro Lastra-Romero, David Brodin, Javier Avila-Carino, Yang Cao, Mikko Airavaara, Per Uhlen, Michael T. Heneka, Marie-Eve Tremblay, Klas Blomgren, Jose L. Venero, Bertrand Joseph
Summary: The molecular diversity of microglia in the CNS has been described. The study shows that microglia expressing the enzyme ARG1 are enriched in phagocytic inclusions and play a role in hippocampal innervation and spine maturation in mice. ARG1-expressing microglia also influence cognition in a sex-dependent manner.
NATURE NEUROSCIENCE
(2023)
Review
Pharmacology & Pharmacy
Ilmari Parkkinen, Anna Their, Muhammad Yasir Asghar, Sreesha Sree, Eija Jokitalo, Mikko Airavaara
Summary: The endoplasmic reticulum plays a crucial role in neuronal functions and is involved in protein processing, calcium regulation, and neuronal activity. Pharmacological regulation of ER calcium can potentially slow down neurodegeneration and provide therapeutic options for degenerative diseases.
PHARMACOLOGICAL REVIEWS
(2023)
Article
Cell Biology
Kuan-Yin Tseng, Vassilis Stratoulias, Wei-Fen Hu, Jui-Sheng Wu, Vicki Wang, Yuan-Hao Chen, Anna Seelbach, Henri J. Huttunen, Natalia Kulesskaya, Cheng-Yoong Pang, Jian-Liang Chou, Maria Lindahl, Mart Saarma, Li-Chuan Huang, Mikko Airavaara, Hock-Kean Liew
Summary: During intracerebral hemorrhage (ICH), hematoma formation leads to local mechanical injury, and the release of hemoglobin and heme induces inflammation and secondary brain injury. Modulating immune cells to promote hematoma resorption and reduce brain edema has potential as a therapeutic strategy for functional recovery after ICH.
CELL DEATH & DISEASE
(2023)
Article
Spectroscopy
Tuomas Mansikkala, Takuji Ohigashi, Miia H. Saloa, Anniina E. Hiltunen, Reetta Vuolteenaho, Petra Sipila, Satu Kuure, Marko Huttula, Johanna Uusimaa, Reetta Hinttala, Ilkka Miinalainen, Salla Kangas, Minna Patanen
Summary: Scanning transmission X-ray microscopy (STXM) in the soft X-ray range is used to study ultrastructural features of mammalian soft tissues, particularly at the carbon 1s edge for label-free soft X-ray spectromicroscopic studies. This technique is promising for studying storage diseases without chemical alteration, although sample preparation is challenging. STXM spectromicroscopic imaging of mouse kidney and liver tissues was conducted, with a focus on ultrastructural abnormalities in genetically modified Slc17a5 mice.
JOURNAL OF ELECTRON SPECTROSCOPY AND RELATED PHENOMENA
(2023)
Article
Biochemistry & Molecular Biology
Tarvi Teder, Jesper Z. Haeggstrom, Mikko Airavaara, Helike Lohelaid
Summary: Hypoxia and tissue damage lead to endoplasmic reticulum stress and neuroinflammation, causing neuronal cell death and neurological impairment in ischemic stroke. Modulating endoplasmic reticulum stress and inflammation can enhance cell survival and protect neurons in ischemic stroke. The interplay between lipid mediators and endoplasmic reticulum stress plays a crucial role in the progression and outcome of ischemic stroke.
PROSTAGLANDINS & OTHER LIPID MEDIATORS
(2023)
Article
Chemistry, Multidisciplinary
Dale W. Prebble, Tanja M. Voser, Safak Er, Irena Hlushchuk, Andrii Domanskyi, Mikko Airavaara, Merrick G. Ekins, George D. Mellick, Anthony R. Carroll
Summary: During a high-throughput screen of Australian marine invertebrate extracts, a marine sponge extract called Clathria (Thalysias) cf. hesperia was found to possess alpha-synuclein binding activity. The purification of this extract led to the identification of 1-methyl-1,2,7,8-tetrahydro-2,8-dioxoadenosine (2) as the alpha-synuclein binder, along with a new compound called hesperine (1) and five other known compounds. In this study, the structure of hesperine (1) was elucidated and the alpha-synuclein binding activity of 1-methyl-1,2,7,8-tetrahydro-2,8-dioxoadenosine (2) was reported.
RESULTS IN CHEMISTRY
(2022)
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)