MNB/DYRK1A is a member of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family that has been strongly conserved across evolution. There are substantial data implicating MNB/DYRK1A in brain development and adult brain function, as well as in neurodegeneration and Down syndrome pathologies. Here we review our current understanding of the neurodevelopmental activity of MNB/DYRK1A. We discuss how MNB/DYRK1A fulfils several sequential roles in neuronal development and the molecular mechanisms possibly underlying these functions. We also summarize the evidence behind the hypotheses to explain how the imbalance in MNB/DYRK1A gene dosage might be implicated in the neurodevelopmental alterations associated with Down syndrome. Finally, we highlight some research directions that may help to clarify the mechanisms and functions of MNB/DYRK1A signalling in the developing brain.
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http://dx.doi.org/10.1111/j.1742-4658.2010.07954.x | DOI Listing |
J Neuroinflammation
January 2025
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
The thrombolytic protease tissue plasminogen activator (tPA) is expressed in the CNS, where it regulates diverse functions including neuronal plasticity, neuroinflammation, and blood-brain-barrier integrity. However, its role in different brain regions such as the substantia nigra (SN) is largely unexplored. In this study, we characterize tPA expression, activity, and localization in the SN using a combination of retrograde tracing and β-galactosidase tPA reporter mice.
View Article and Find Full Text PDFBMC Med Genomics
January 2025
Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK.
Amyotrophic lateral sclerosis (ALS) lacks a specific biomarker, but is defined by relatively selective toxicity to motor neurons (MN). As others have highlighted, this offers an opportunity to develop a sensitive and specific biomarker based on detection of DNA released from dying MN within accessible biofluids. Here we have performed whole genome bisulfite sequencing (WGBS) of iPSC-derived MN from neurologically normal individuals.
View Article and Find Full Text PDFJ Headache Pain
January 2025
Sensory Biology Unit, Translational Research Center, Rigshospitalet, Glostrup, Denmark.
Objective: The neuropeptide calcitonin gene-related peptide (CGRP) has been established to be a key signaling molecule in migraine, but little is known about the differences between the two isoforms: αCGRP and βCGRP. Previous studies have been hampered by their close similarity, making the development of specific antibodies nearly impossible. In this study we sought to test the hypothesis that αCGRP and βCGRP localize differently within the neurons of the mouse trigeminal ganglion (TG), using αCGRP knock out (KO) animals.
View Article and Find Full Text PDFCommun Biol
January 2025
Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX, USA.
Aggregation of microtubule-associated tau protein is a distinct hallmark of several neurodegenerative disorders such as Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and progressive supranuclear palsy (PSP). Tau oligomers are suggested to be the primary neurotoxic species that initiate aggregation and propagate prion-like structures. Furthermore, different diseases are shown to have distinct structural characteristics of aggregated tau, denoted as polymorphs.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Cortical interneurons generated from ganglionic eminence via a long-distance journey of tangential migration display evident cellular and molecular differences across brain regions, which seeds the heterogeneous cortical circuitry in primates. However, whether such regional specifications in interneurons are intrinsically encoded or gained through interactions with the local milieu remains elusive. Here, we recruit 685,692 interneurons from cerebral cortex and subcortex including ganglionic eminence within the developing human and macaque species.
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