Neurotrauma in the form of traumatic brain injury (TBI) afflicts more Americans annually than Alzheimer's and Parkinson's disease combined, yet few researchers have used neuroproteomics to investigate the underlying complex molecular events that exacerbate TBI. Discussed in this review is the methodology needed to explore the neurotrauma proteome-from the types of samples used to the mass spectrometry identification and quantification techniques available. This neuroproteomics survey presents a framework for large-scale protein research in neurotrauma, as applied for immediate TBI biomarker discovery and the far-reaching systems biology understanding of how the brain responds to trauma. Ultimately, knowledge attained through neuroproteomics could lead to clinical diagnostics and therapeutics to lessen the burden of neurotrauma on society.
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http://dx.doi.org/10.1002/mas.20073 | DOI Listing |
Mol Neurodegener
December 2024
German Center for Neurodegenerative Diseases (LMU), Klinikum, Germany.
Background: The prion-like spreading of Tau pathology is the leading cause of disease progression in various tauopathies. A critical step in propagating pathologic Tau in the brain is the transport from the extracellular environment and accumulation inside naïve neurons. Current research indicates that human neurons internalize both the physiological extracellular Tau (eTau) monomers and the pathological eTau aggregates.
View Article and Find Full Text PDFMethods Mol Biol
December 2024
Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil.
This chapter presents an optimized method for isolating synaptic vesicles (SVs) from neurospheres derived from human induced pluripotent stem cells (hiPSCs). The protocol begins with neurosphere cultivation to achieve mature neurons, which is essential for the functional studies of neuronal activity. Following this, neurosphere-derived synaptosomes are isolated, and SVs are enriched through differential centrifugation.
View Article and Find Full Text PDFBrain
December 2024
Lab of Parkinson's & Other Movement Disorders, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS); Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona; Institut de Neurociències, Universitat de Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) CB06/05/0018-ISCIII; ES 08036 Barcelona, Spain.
Leucine-rich repeat kinase 2 (LRRK2) inhibition is a promising disease-modifying therapy for LRRK2-associated Parkinson's disease (L2PD) and idiopathic PD (iPD). However, pharmaco-dynamic readouts and progression biomarkers for clinical trials aiming for disease modification are insufficient since no endogenous marker reflecting enhanced kinase activity of the most common LRRK2 G2019S mutation has been reported yet in L2PD patients. Employing phospho-/proteomic analyses we assessed the impact that LRRK2 activating mutations had in peripheral blood mononuclear cells (PBMCs) from a LRRK2 clinical cohort from Spain (n=174).
View Article and Find Full Text PDFNeurology
January 2025
From the Perioperative, Acute, Critical Care and Emergency Medicine (PACE) (D.P.W., D.M., V.F.J.N.), Department of Medicine, University of Cambridge, Addenbrooke's Hospital; Division of Psychology (L.W.), University of Stirling, United Kingdom; Department of Neurosurgery (E.C.), Medical School, and Neurotrauma Research Group (E.C.), Szentagothai Research Centre, University of Pecs, Hungary; Department of Neurosurgery (A.B.), Faculty of Medicine and Health, Örebro University, Sweden; Department of Neurobiology (K.K.W.W.), Center for Neurotrauma, Multiomics & Biomarkers (CNMB) Neuroscience Institute, Morehouse School of Medicine (MSM), Atlanta, GA; Program for Neurotrauma, Neuroproteomics and Biomarker Research (K.K.W.W.), Departments of Emergency Medicine, Psychiatry and Neuroscience, University of Florida, McKnight Brain Institute, Gainesville; Institute of Psychology (N.v.S., M.Z.), University of Innsbruck; Faculty of Psychotherapy Science (M.Z.), Sigmund Freud University, Vienna, Austria; Department of Biomedical Data Sciences (E.S.), Leiden University Medical Center, the Netherlands; Department of Neurosurgery (A.I.R.M.), Antwerp University Hospital, Edegem; and Department of Translational Neuroscience (A.I.R.M.), Faculty of Medicine and Health Science, University of Antwerp, Belgium.
Background And Objectives: There is seemingly contradictory evidence concerning relationships between day-of-injury biomarkers and outcomes after mild traumatic brain injury (mTBI). To address this issue, we examined the association between a panel of biomarkers and multidimensional TBI outcomes.
Methods: Participants with mTBI (Glasgow coma scores [GCSs] 13-15) were selected from Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury, a European observational study recruiting patients with TBI with indication for brain CT and presentation within 24 hours.
Mol Psychiatry
December 2024
Department of Psychiatry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
Dysfunctional glial cells play a pre-eminent role in schizophrenia pathophysiology. Post-mortem studies have provided evidence for significantly decreased glial cell numbers in different brain regions of individuals with schizophrenia. Reduced glial cell numbers are most pronounced in oligodendroglia, but reduced astrocyte cell densities have also been reported.
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