Article
Developmental Biology
Aliia Murtazina, Igor Adameyko
Summary: The peripheral nervous system is a heterogeneous system with diverse functions, including communication between the brain and the body, control of development and regeneration. It can be divided into sensory, motor, autonomic and enteric domains. Recent advances in single-cell transcriptomics have revealed new neuronal subtypes and improved cell-type classifications. This article discusses the roles, origin and heterogeneity of the peripheral nervous system, highlighting recent discoveries and future perspectives.
Article
Developmental Biology
Aya Mikdache, Marie-Jose Bouied, Emilie Lesport, Brigitte Delespierre, Julien Loisel-Duwattez, Cindy Degerny, Marcel Tawk
Summary: This study demonstrates the crucial role of timely division of Schwann cells in mediating laminin expression to orchestrate radial sorting and peripheral myelination.
Article
Neurosciences
Haley Jeanette, Leandro N. Marziali, Urja Bhatia, Abigail Hellman, Jacob Herron, Ashley M. Kopec, Maria Laura Feltri, Yannick Poitelon, Sophie Belin
Summary: YAP and TAZ, effectors of the Hippo pathway, play a regulatory role in the proliferation and differentiation of repair Schwann cells during peripheral nerve regeneration, contributing to remyelination over time.
Review
Biochemistry & Molecular Biology
Civia Z. Chen, Bjorn Neumann, Sarah Forster, Robin J. M. Franklin
Summary: Myelin sheaths are crucial for neuronal function by supporting axonal integrity and rapid impulse conduction. In response to demyelinating injuries in the CNS, OPCs can undergo remyelination. OPCs might be a major source of CNS-resident SCs, which could be an attractive target for promoting endogenous remyelination.
Article
Neurosciences
Yoshinori Otani, Akihiro Taguchi, Keisuke Hamada, Yoshio Hayashi, Yoshihide Yamaguchi, Hiroko Baba
Summary: Translational readthrough-inducing agents have been developed to treat nonsense mutations in hereditary diseases. This study evaluated the activities of novel negamycin-derived readthrough agents and their impact on the sciatic nerve. The results showed that these agents enhanced programmed translational readthrough and had less damaging effects on the nerve compared to traditional readthrough agents.
Article
Neurosciences
Natasha Sukhanov, Anya Vainshtein, Yael Eshed-Eisenbach, Elior Peles
Summary: Cell adhesion proteins of the Cadm family play a crucial role in myelination and axonal organization. The study reveals that Cadm3 is the main axonal ligand for glial Cadm4, and the combined action of Cadm2 and Cadm1 can compensate for its absence. Genetic ablation of all three Cadm genes phenocopies the abnormalities detected in the absence of Cadm4, indicating their interplay in regulating myelination and axonal organization.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Medicine, Research & Experimental
Yuxia Sun, Xiang Chen, Cen Yue, Wenyi Yang, Shu Zhang, Zhimin Ou, Ying Chen
Summary: This study showed that Ninj2 acts as a negative regulator in controlling Schwann cell (SC) development in the peripheral nervous system (PNS). Loss of Ninj2 promotes myelination and accelerates the remyelination process. Ninj2 interacts with ITGB1 to inhibit laminin-integrin signaling, affecting myelination process.
Article
Biochemistry & Molecular Biology
Jose A. Gomez-Sanchez, Nikiben Patel, Fernanda Martirena, Shaline Fazal, Clara Mutschler, Hugo Cabedo
Summary: The peripheral nervous system (PNS) has superior regenerative capacity compared to the central nervous system (CNS). This regenerative ability is attributed to the reprogramming of Schwann cells (SC) into repair Schwann cells, which support axonal growth, myelin degradation, neurotrophic factor secretion, and axonal growth guidance. Epigenetic regulations, particularly histone acetylation and deacetylation, play a crucial role in SC reprogramming and nerve regeneration. This review focuses on Zn2+-dependent histone deacetylases (HDACs) and their importance in repair SC biology and remyelination after PNS injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Madoka Koyanagi, Satoshi Imai, Yuki Iwamitsu, Mayuna Matsumoto, Mamiko Saigo, Akari Moriya, Takashi Ogihara, Yui Nakazato, Atsushi Yonezawa, Shunsaku Nakagawa, Takayuki Nakagawa, Kazuo Matsubara
Summary: This study identified cilostazol as a potential therapeutic for CIPN, with the ability to suppress paclitaxel-induced Schwann cell dedifferentiation. Cilostazol promoted Schwann cell differentiation through cAMP/Epac signaling and prevented demyelination and hypersensitivity in models of CIPN. Additionally, cilostazol did not compromise the anticancer properties of paclitaxel, highlighting its potential utility as a causal therapeutic for CIPN.
Article
Materials Science, Multidisciplinary
Sunghee Estelle Park, Jinchul Ahn, Hyo-Eun Jeong, Inchan Youn, Dongeun Huh, Seok Chung
Summary: The study presented an in vitro model of the peripheral nervous system (PNS) by establishing a coculture model of motor neurons (MNs) and Schwann cells (SCs) in a 3D extracellular matrix hydrogel scaffold. The model successfully reproduced myelination process in the PNS and demonstrated the potential to manipulate myelination and demyelination processes in motor neuron diseases.
NPG ASIA MATERIALS
(2021)
Review
Neurosciences
Chengxiao Ma, Wen Zhang, Maohong Cao
Summary: While most studies on Parkinson's disease have focused on the central nervous system, recent research has highlighted the importance of the peripheral nervous system, particularly in understanding non-motor symptoms associated with the disease. Abnormalities in alpha-synuclein deposition and neuroinflammation in the PNS have been identified, leading to potential implications for clinical diagnosis and treatment of PD.
FRONTIERS IN NEUROSCIENCE
(2021)
Review
Clinical Neurology
Alessandra Bolino
Summary: Myelin, formed by the plasma membrane of glial cells, insulates axons in the nervous system of vertebrates and plays a crucial role in speeding up electric signal transmission and influencing axonal metabolism and neural circuit plasticity. By studying Schwann cells and their myelination process, as well as human disorders related to myelination, researchers have significantly advanced our understanding of myelin biology.
Article
Developmental Biology
Joana Paes de Faria, Raquel S. Vale-Silva, Reinhard Fassler, Hauke B. Werner, Joao B. Relvas
Summary: Pinch2 plays a crucial role in central nervous system myelination, preventing excessive myelin wrapping and promoting myelin stability. Loss of Pinch2 results in hypermyelination and pathological myelin outfoldings.
Article
Immunology
Florian Mayrhofer, Angela M. M. Hanson, Manuel F. F. Navedo, Yang K. K. Xiang, Athena M. M. Soulika, Wenbin Deng, Olga V. V. Chechneva
Summary: Material transfer is an important way for cells to exchange information and resources. It has been found that neurons in the mouse central nervous system can receive nuclear and ribosomal material from Sox10-lineage cells. This transfer of material is region dependent, develops during postnatal brain maturation, and responds dynamically to LPS-induced neuroinflammation in adult mice. These findings have potential implications for understanding and modulating neuronal function, as well as treating neurological disorders.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Neurosciences
Akihiro Ishii, Miki Furusho, Rashmi Bansal
Summary: Multiple intracellular signaling pathways, including Mek/ERK1/2-MAPK and PI3K/Akt/mTOR, are involved in regulating myelination in the peripheral nervous system. The roles of these pathways may differ during development and adulthood, highlighting the complexity of their interactions in Schwann cells.
Article
Genetics & Heredity
Roope A. Kallionpaa, Kaisa Ahramo, Marianna Aaltonen, Paula Pennanen, Juha Peltonen, Sirkku Peltonen
Summary: The study investigated the levels of circulating free plasma DNA (cfDNA) in NF1 patients and healthy controls, finding that NF1 may have a limited impact on cfDNA levels, likely not affecting the use of cfDNA-based assays.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Genetics & Heredity
Edvard Johansson, Roope A. Kallionpaa, Petri Bockerman, Juha Peltonen, Sirkku Peltonen
Summary: NF1 is associated with reduced educational attainment, with individuals more likely to pursue vocational education. History of cancer and developmental disorders are major predictors of lack of secondary education. NF1 decreases the attainment of Bachelor's and Master's degrees.
Article
Biochemistry & Molecular Biology
Paula Pennanen, Roope A. Kallionpaa, Sirkku Peltonen, Liisa Nissinen, Veli-Matti Kahari, Eetu Heerva, Juha Peltonen
Summary: This study evaluated the roles of various signaling pathways in human osteoclast differentiation and found that inhibiting most pathways decreased osteoclast numbers and disrupted morphology, with p38 inhibition unexpectedly increasing osteoclast numbers. The Ras inhibitor FTS had differing effects on control and NF1 samples, while MEK, PI3K, and mTOR inhibition reduced NF1 osteoclast numbers significantly. Overall, the results highlight the complexity of osteoclastogenesis regulation by multiple pathways and underscore the differences between murine and human findings in this process.
MOLECULAR BIOLOGY REPORTS
(2021)
Article
Dermatology
Roope A. Kallionpaa, Kaisa Ahramo, Eija Martikkala, Elnaz Fazeli, Pekka Haapaniemi, Anne Rokka, Ilmo Leivo, Ilkka T. Harvima, Juha Peltonen, Sirkku Peltonen
Summary: The results highlight the abundance of mast cells in cNFs and that their number and subtypes clearly differ from those previously reported in unaffected skin.
Article
Allergy
Eeva Sliz, Laura Huilaja, Anu Pasanen, Triin Laisk, Ene Reimann, Reedik Magi, Katariina Hannula-Jouppi, Sirkku Peltonen, Teea Salmi, Leena Koulu, Kaisa Tasanen, Johannes Kettunen
Summary: This study aimed to gain a better understanding of the genetic contribution to atopic dermatitis (AD) risk by utilizing biobank resources. Through a genome-wide meta-analysis, the researchers identified 30 loci associated with AD, including 5 novel loci. Two of the novel loci were found to have missense mutations in genes crucial to the integrity and strength of the epidermis. These findings provide insights into novel genetic pathways involved in AD pathophysiology and potential opportunities for future treatment strategies.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Genetics & Heredity
Sirkku Peltonen, Arnaud Jannic, Pierre Wolkenstein
Summary: Cutaneous neurofibromas are a hallmark of neurofibromatosis 1 and can cause pain and itch for patients. The use of CO2 laser for cNF removal has been shown to be a feasible treatment option in clinical practice.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2022)
Article
Genetics & Heredity
Edvard Johansson, Roope A. Kallionpaa, Petri Bockerman, Sirkku Peltonen, Juha Peltonen
Summary: This study investigated the impact of neurofibromatosis 1 (NF1) on economic well-being and found that individuals with NF1 had worse economic outcomes compared to those without NF1. The effect of NF1 on economic well-being was partially explained by factors such as low education, increased morbidity, and reduced labor market participation. NF1 had a larger negative effect on income from work than on total income, indicating partial compensation from the Finnish social security system. The study also found that NF1 had a greater impact on economic inequality for men than for women.
GENETICS IN MEDICINE
(2022)
Article
Oncology
Pegah Rahmati Nezhad, Pilvi Riihilae, Jaakko S. Knuutila, Kristina Viiklepp, Sirkku Peltonen, Markku Kallajoki, Seppo Meri, Liisa Nissinen, Veli-Matti Kahari
Summary: The most common metastatic skin cancer, cutaneous squamous cell carcinoma (cSCC), is growing worldwide, and there are no biomarkers or therapeutic targets for high-risk cSCCs. Recent studies have identified the essential role of autocrine complement synthesis in cSCC progression. This study evaluates the role of complement Factor D (FD), the rate-limiting enzyme of the alternative complement pathway, in cSCC development. The results identify FD as a novel biomarker and potential therapeutic target for cSCC, and propose the small-molecule FD inhibitor Danicopan as a highly specific drug candidate in the therapy of advanced cSCC. Discovery of complement-associated molecular markers for cSCC progression would improve diagnosis, classification, prognostication, and targeted therapy of cSCC and its precursors in the future.
Article
Neurosciences
Salla M. Kangas, Jaakko Teppo, Maija J. Lahtinen, Anu Suoranta, Bishwa Ghimire, Pirkko Mattila, Johanna Uusimaa, Markku Varjosalo, Jani Katisko, Reetta Hinttala
Summary: This study presents an improved method for collecting fresh brain tissue samples from surgical instruments used in deep brain stimulation (DBS) procedures. The collected tissues were used for transcriptomic and proteomic analyses. The results indicate that the surgical instruments retain sufficient brain material for protein and gene expression studies, and the approach is robust and reproducible.
TRANSLATIONAL NEURODEGENERATION
(2022)
Article
Pediatrics
Paula L. Keskitalo, Salla M. Kangas, Sirja Sard, Tytti Pokka, Virpi Glumoff, Petri Kulmala, Paula Vahasalo
Summary: This study found that MRP8/14 levels can predict disease progression in patients with new-onset JIA, and P-MRP8/14 may be more effective in assessing disease activity compared to S-MRP8/14.
PEDIATRIC RHEUMATOLOGY
(2022)
Article
Dermatology
Rahime Inci, Theofanis Zagoras, Despoina Kantere, Peter Holmstrom, Martin Gillstedt, Sam Polesie, Sirkku Peltonen
Summary: Porokeratosis is a common genodermatosis that is associated with an increased risk of skin cancer.
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2023)
Article
Neurosciences
Dani Flinkman, Ye Hong, Jelena Gnjatovic, Prasannakumar Deshpande, Zsuzsanna Ortutay, Sirkku Peltonen, Valtteri Kaasinen, Peter James, Eleanor Coffey
Summary: Deficits in protein synthesis are associated with Parkinson's disease (PD). We conducted a study to identify the specific proteins affected and differences in synthesis between sporadic and LRRK2-G2019S PD patients. Through proteomic analysis, we found that regulators of endo-lysosomal sorting, mRNA processing, and components of the translation machinery were consistently low in both sporadic and LRRK2-G2019S PD patients. This study provides valuable insights into the dysregulation of proteostasis in PD.
NPJ PARKINSONS DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Roope A. Kallionpaa, Edvard Johansson, Petri Bockerman, Juha Peltonen, Sirkku Peltonen
Summary: Neurofibromatosis 1 (NF1) is a multisystem disorder associated with a high risk for cancer, behavioral and cognitive deficits, low educational attainment, and decreased income. This study analyzed labor market participation in individuals with NF1 in Finland and found that they had significantly fewer working days per year, higher unemployment, and more sickness absence compared to a control group. The causes of sickness absence were consistent with the morbidity profile of NF1. Overall, NF1 significantly interferes with labor market participation through both unemployment and morbidity.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
