Article
Multidisciplinary Sciences
Matthijs C. Dorst, Maria Diaz-Moreno, David O. Dias, Eduardo L. Guimaraes, Daniel Holl, Jannis Kalkitsas, Gilad Silberberg, Christian Goritz
Summary: Research has shown that inhibition of Notch signaling in astrocytes can induce adult striatal neurogenesis in the intact mouse brain. These astrocyte-derived neurons possess distinct electrophysiological properties, constituting the only glutamatergic striatal population, and have the potential to compensate for reduced neuronal activity in the striatal circuitry caused by aging or lesion-induced neuronal loss.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell & Tissue Engineering
So-Young Lee, Hyun-Ju An, Jin Man Kim, Min-Ji Sung, Do Kyung Kim, Hyung Kyung Kim, Jongbeom Oh, Hye Yun Jeong, Yu Ho Lee, Taeyoung Yang, Jun Han Kim, Ha Jeong Lim, Soonchul Lee
Summary: PINK1 is critical for mitochondrial quality control and decreasing reactive oxygen species production during osteoblast differentiation. Inhibition of PINK1 leads to impaired osteoblast differentiation and defects in mitochondrial homeostasis, while activation of PINK1 may be a potential treatment target for bone diseases.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Cell & Tissue Engineering
Kristi Dietert, Swetha Mahesula, Sheetal Hegde, John Verschelde, Pamela Reed, Shane Sprague, Erzsebet Kokovay, Naomi L. Sayre
Summary: After ischemia, SDF1 upregulates in brain parenchyma cells, promoting the migration of adult neural stem cells to the injury site through the CXCR4 receptor. We identified LRP1 as a novel regulator of CXCR4 in neural stem cells and observed disrupted neural stem cell migration in vitro and reduced localization to the lesion in LRP1 knockout mice. Our findings suggest that the interaction between LRP1 and CXCR4 could have significant implications for neural stem cell physiology.
Article
Cell Biology
Soni Deshwal, Mashun Onishi, Takashi Tatsuta, Tim Bartsch, Eileen Cors, Katharina Ried, Kathrin Lemke, Hendrik Nolte, Patrick Giavalisco, Thomas Langer
Summary: The cytosolic lipid transfer protein STARD7 is identified as a critical factor for intracellular coenzyme Q transport and suppresses ferroptosis. Dual localization of STARD7 to mitochondria and cytosol ensures the synthesis of coenzyme Q and its transport to the plasma membrane. PARL-mediated STARD7 processing is necessary for coordinating coenzyme Q synthesis and cellular distribution and could be targeted to interfere with ferroptosis.
NATURE CELL BIOLOGY
(2023)
Article
Neurosciences
Mingmei Wang, Chunlei Wan, Tao He, Chaojun Han, Kailian Zhu, John L. Waddington, Xuechu Zhen
Summary: Mitochondria play a crucial role in Parkinson's disease, and mitophagy is essential for the survival of DA neurons. The sigma-1 receptor modulates mitophagy, providing protection for DA neurons in a PD-like mouse model.
Article
Medicine, Research & Experimental
Kuo Zhang, Fan Wang, Mengying Zhai, Meiyao He, Yuxuan Hu, Lijin Feng, Yuting Li, Jingyu Yang, Chunfu Wu
Summary: Chronic stress can induce depressive-like behavior and inhibit adult hippocampal neurogenesis. Chronic corticosterone treatment decreases the proliferation and survival of neural stem cells, impairs the migration of newborn neurons, and increases neuronal autophagy. Inhibiting hyperactive neuronal autophagy can reverse the decrease in neuronal brain-derived neurotrophic factor levels, rescue neurogenesis, and exert antidepressant effects.
Article
Neurosciences
Amanda R. Burmeister, Juozas Gordevicius, Emmanuel N. Paul, Christina Houck, Sonia George, Martha L. Escobar Galvis, Qiong Sha, Patrik Brundin, J. Andrew Pospisilik, Karen Racicot, Lena Brundin
Summary: In this study, a mouse maternal infection model was used to investigate the impact of maternal herpesvirus infection on the development and physiology of midbrain dopaminergic neurons in adult offspring. The results suggested that maternal infection with Herpesviridae, specifically MHV68, can trigger changes in midbrain development that affect dopamine neuron physiology in adulthood. This study is important for understanding the neuronal susceptibility underlying neurodegenerative diseases, particularly Parkinson's disease.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Multidisciplinary Sciences
Melissa Vos, Marija Dulovic-Mahlow, Frida Mandik, Lisa Frese, Yuliia Kanana, Sokhna Haissatou Diaw, Julia Depperschmidt, Claudia Boehm, Jonas Rohr, Thora Lohnau, Inke R. Koenig, Christine Klein
Summary: The study reveals the crucial role of ceramide in PINK1-related Parkinson's disease and indicates that adjusting lipid metabolism can improve mitochondrial function, highlighting the connection between ceramide and mitochondria in the pathophysiology of PD.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Karla Sanchez-Huerta, Rosaura Debbie Saldana-Salinas, Pablo Edson Bustamante-Nieves, Adriana Jimenez, Alejandro Corzo-Cruz, Marina Martinez-Vargas, Rosalinda Guevara-Guzman, Ivan Velasco, Enrique Estudillo
Summary: This study found that sucrose intake during late adolescence does not induce anxiety, but does increase cell proliferation in the ventral dentate gyrus. Although there were no differences in the number of immature granular neurons in the hippocampus of rats exposed to sucrose, more immature neurons with impaired dendritic orientation were observed in both groups exposed to sucrose.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Chengcheng Xu, Yao Wu, Lili Tang, Yan Liang, Yang Zhao
Summary: The study demonstrates that Cistanoside A (CA) has neuroprotective effects against Parkinson's disease (PD) by promoting the PINK1/Parkin/p62 pathway to accelerate the degradation of damaged mitochondria, reducing oxidative stress.
BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
(2023)
Editorial Material
Cell Biology
Melissa Vos, Christine Klein
Summary: PINK1 plays a critical role in the pathogenesis of Parkinson's disease, connecting to both mitophagy and energy production. Accumulation of ceramide in mitochondria triggers ceramide-induced mitophagy, while negatively affecting SS-oxidation.
Article
Multidisciplinary Sciences
Naomi Oka, Kazuya Shimada, Azusa Ishii, Nobuyuki Kobayashi, Kazuhiro Kondo
Summary: Neurological complications in SARS-CoV-2 infection, including olfactory dysfunction, brain inflammation, malaise, and depressive symptoms, may contribute to long COVID. However, the direct evidence of central nervous system damage caused by SARS-CoV-2 proliferation is usually absent in autopsies of COVID-19 patients. Therefore, the pathogenesis mechanisms of these symptoms remain largely unknown. By expressing SARS-CoV-2 S1 protein in mouse nasal cavities, increased apoptosis of the olfactory system and decreased acetylcholine production in the brain were observed. The decrease in acetylcholine production was associated with brain inflammation, malaise, depressive clinical signs, and reduced expression of the cytokine degrading factor ZFP36. Administering the cholinesterase inhibitor donepezil to the mice improved brain inflammation, malaise, and depressive clinical signs. These findings provide insight into the pathogenesis mechanisms of neurological complications associated with COVID-19 and long COVID.
Article
Neurosciences
Sara Bottes, Baptiste N. Jaeger, Gregor-Alexander Pilz, David J. Jorg, John Darby Cole, Merit Kruse, Lachlan Harris, Vladislav Korobeynyk, Izaskun Mallona, Fritjof Helmchen, Francois Guillemot, Benjamin D. Simons, Sebastian Jessberger
Summary: Researchers identified long-term self-renewing neural stem cells (NSCs) in the adult mouse hippocampus using intravital imaging and single-cell RNA sequencing. They found that Gli1-targeted NSCs exhibit long-term self-renewal, while Ascl1-targeted NSCs have limited proliferative activity before exhaustion. The study revealed the existence of heterogeneous NSC populations with diverse behavioral properties in contributing to neurogenesis in the adult hippocampus.
NATURE NEUROSCIENCE
(2021)
Article
Cell Biology
Lisa Schwarz, Julia C. Fitzgerald
Summary: The Miro1 S156A mutation leads to a significant depletion of Miro1 protein levels, a slight increase in mitochondrial mass, and slightly lengthened mitochondria. This mutation also causes a significant reduction in mitochondrial oxygen consumption, accompanied by a depletion of OXPHOS complexes III and V.
Article
Multidisciplinary Sciences
Dingbang Ma, Nicholas Herndon, Jasmine Quynh Le, Katharine C. Abruzzi, Kai Zinn, Michael Rosbash
Summary: Our recent single-cell sequencing of adult Drosophila circadian neurons revealed unexpected heterogeneity and cell-specific expression of neuron communication molecules. Similar heterogeneity was observed in adult brain dopaminergic neurons. The common features of these neurons play essential roles in neuronal identity, connectivity, and the complex behavioral repertoire of Drosophila.
Article
Clinical Neurology
Semra Smajic, Cesar A. Prada-Medina, Zied Landoulsi, Jenny Ghelfi, Sylvie Delcambre, Carola Dietrich, Javier Jarazo, Jana Henck, Saranya Balachandran, Sinthuja Pachchek, Christopher M. Morris, Paul Antony, Bernd Timmermann, Sascha Sauer, Sandro L. Pereira, Jens C. Schwamborn, Patrick May, Anne Gruenewald, Malte Spielmann
Summary: In this study, the contribution of different cell types to Parkinson's disease pathology was investigated using single-nuclei RNA sequencing. The results revealed a disease-specific neuronal cell cluster and changes in glial cells, as well as the enrichment of Parkinson's disease risk genes. These findings highlight the importance of inflammatory signaling and immunomodulatory treatments in Parkinson's disease.
Article
Clinical Neurology
Javier Jarazo, Kyriaki Barmpa, Jennifer Modamio, Claudia Saraiva, Sonia Sabate-Soler, Isabel Rosety, Anne Griesbeck, Florian Skwirblies, Gaia Zaffaroni, Lisa M. Smits, Jihui Su, Jonathan Arias-Fuenzalida, Jonas Walter, Gemma Gomez-Giro, Anna S. Monzel, Xiaobing Qing, Armelle Vitali, Gerald Cruciani, Ibrahim Boussaad, Francesco Brunelli, Christian Jager, Aleksandar Rakovic, Wen Li, Lin Yuan, Emanuel Berger, Giuseppe Arena, Silvia Bolognin, Ronny Schmidt, Christoph Schroeder, Paul M. A. Antony, Christine Klein, Rejko Kruger, Philip Seibler, Jens C. Schwamborn
Summary: This study investigated the differences between neurons derived from Parkinson's disease patients and controls, identifying potential pathways for targeted treatment. By correcting mutations and using a specific compound, improvements in metabolic properties and neuronal differentiation in patient-derived cells were observed. Treatment with a repurposed compound was shown to restore impaired dopaminergic differentiation in Parkinson's disease patient-derived cells.
MOVEMENT DISORDERS
(2022)
Article
Neurosciences
Sonia Sabate-Soler, Sarah Louise Nickels, Claudia Saraiva, Emanuel Berger, Ugne Dubonyte, Kyriaki Barmpa, Yan Jun Lan, Tsukasa Kouno, Javier Jarazo, Graham Robertson, Jafar Sharif, Haruhiko Koseki, Christian Thome, Jay W. Shin, Sally A. Cowley, Jens C. Schwamborn
Summary: The absence of microglia in current midbrain organoid systems limits the study of neuronal networks and neuroinflammation-related diseases. This study successfully derived microglia from human iPSCs and integrated them into midbrain organoids, shedding light on the role of microglia in influencing other cells in the organoids.
Article
Clinical Neurology
Kobi Wasner, Semra Smajic, Jenny Ghelfi, Sylvie Delcambre, Cesar A. Prada-Medina, Evelyn Knappe, Giuseppe Arena, Patrycja Mulica, Gideon Agyeah, Aleksandar Rakovic, Ibrahim Boussaad, Katja Badanjak, Jochen Ohnmacht, Jean-Jacques Gerardy, Masashi Takanashi, Joanne Trinh, Michel Mittelbronn, Nobutaka Hattori, Christine Klein, Paul Antony, Philip Seibler, Malte Spielmann, Sandro L. Pereira, Anne Gruenewald
Summary: “Parkin plays a crucial role in regulating mitophagy, mitochondrial biogenesis, and mtDNA maintenance, protecting midbrain neurons from neuroinflammation and degeneration.”
MOVEMENT DISORDERS
(2022)
Article
Biology
Christina Wolf, Alireza Pouya, Sara Bitar, Annika Pfeiffer, Diones Bueno, Sabine Arndt, Stefan Tenzer, Federica Dal Bello, Caterina Vianello, Sandra Ritz, Jonas Schwirz, Kristina Dobrindt, Michael Peitz, Eva-Maria Hanschmann, Ibrahim Boussaad, Oliver Brustle, Marta Giacomello, Rejko Kruger, Axel Methner, Liliana Rojas-Charry, David Gomez-Zepeda, Pauline Mencke, Marion Silies, Oliver Brustle
Summary: GDAP1 mutations in Charcot-Marie-Tooth disease 4A inhibit the pyruvate dehydrogenase complex and restrict the localization of dynamin-related protein 1 in mitochondria through alterations of actin signaling. This study provides insights into the underlying mechanism of GDAP1-associated phenotypes and highlights the role of disrupted actin signaling in CMT4A pathophysiology.
COMMUNICATIONS BIOLOGY
(2022)
Article
Cell & Tissue Engineering
Pauline Mencke, Zoe Hanss, Javier Jarazo, Francois Massart, Arkadiusz Rybicki, Elizabet Petkovski, Enrico Glaab, Ibrahim Boussaad, Vincenzo Bonifati, Jens Christian Schwamborn, Wim Mandemakers, Rejko Krueger
Summary: In this study, an isogenic control cell line was generated using CRISPR/Cas9 technology to correct the disease-causing mutation in the PARK7 gene in a Parkinson's disease patient. This cell line will be used for phenotype analysis of neurons and astrocytes derived from the patient.
STEM CELL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Beatriz Garcia Santa Cruz, Jan Slter, Gemma Gomez-Giro, Claudia Saraiva, Sonia Sabate-Soler, Jennifer Modamio, Kyriaki Barmpa, Jens Christian Schwamborn, Frank Hertel, Javier Jarazo, Andreas Husch
Summary: The study focuses on addressing the challenges of data acquisition and image analysis in complex disease research. By combining traditional computer vision methods with deep learning, the research team successfully trained a deep learning network and improved the segmentation quality using automatically generated labels. The user-friendly graphical interface allows researchers to evaluate and correct the predictions. Furthermore, the study demonstrates the feasibility of training a deep learning solution on a large dataset of noisy labels.
SCIENTIFIC REPORTS
(2022)
Review
Cell Biology
Arianna Minoia, Luca Dalle Carbonare, Jens Christian Schwamborn, Silvia Bolognin, Maria Teresa Valenti
Summary: Degenerative diseases affecting bone tissues and the brain have significant socioeconomic impact. Osteoporosis and neurodegenerative diseases are often linked, with bone fractures and reduced mobility being common in patients. Bone is not only involved in movement but also plays a role in mineral metabolism and the production of stem cells. The interaction between the nervous system and bone is bidirectional, with bone influencing neuronal regulation and vice versa. This review summarizes recent knowledge on this interaction and emphasizes its importance. Experimental models and suggestions for evaluating molecular interactions between nerve and skeletal cells are also discussed.
Article
Cell Biology
Maria Meszaros, Thi Ha My Phan, Judit P. Vigh, Gergo Porkolab, Anna Kocsis, Emese K. Pali, Tamas F. Polgar, Fruzsina R. Walter, Silvia Bolognin, Jens C. Schwamborn, Jeng-Shiung Jan, Maria A. Deli, Szilvia Veszelka
Summary: Research has found that nanoparticles targeting cerebral endothelial cells can enhance drug delivery to the brain. By combining alanine and glutathione, these polypeptide nanocarriers showed increased permeability and cellular uptake in a co-culture model of human endothelial cells and brain pericytes. These findings suggest that poly(l-glutamic acid) nanoparticles can be effective nanocarriers for drug delivery to the nervous system.
Article
Cell & Tissue Engineering
Axel Chemla, Giuseppe Arena, Claudia Saraiva, Clara Berenguer-Escuder, Dajana Grossmann, Anne Grunewald, Christine Klein, Philip Seibler, Jens C. Schwamborn, Rejko Kruger
Summary: In this study, two Parkinson's disease patients' primary skin fibroblasts carrying distinct heterozygous mutations in the RHOT1 gene encoding Miro1 were reprogrammed into induced pluripotent stem cells (iPSCs) using episomal reprogramming. Isogenic gene-corrected lines were generated using CRISPR/Cas9 technology. Both isogenic pairs were comprehensively characterized and quality assured to study the Miro1-related molecular mechanisms underlying neurodegeneration in iPSC-derived neuronal models.
STEM CELL RESEARCH
(2023)
Article
Medicine, Research & Experimental
Manuela Cassotta, Hugo Geerts, Lise Harbom, Tiago F. Outeiro, Iosif Pediaditakis, Orly Reiner, Stefan Schildknecht, Jens C. Schwamborn, Jarrod Bailey, Kathrin Herrmann, Helena T. Hogberg
Summary: Parkinson's disease (PD) is a complex neurodegenerative condition with a lack of preventive or curative therapies. New approach methodologies (NAMs) hold potential to advance PD research and reduce the reliance on animal-based studies. Key recommendations to advance PD research include integrating NAMs, learning from other neurodegenerative diseases, increasing data sharing, promoting innovative pilot studies, and accessing philanthropic funding.
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
(2022)