Biology subjects

Abdelmageed, M.

Publications and source records attributed to Abdelmageed, M..

4 recordsLinked to original sources

bioRxiv2026

Neuronal and vascular genome-maintenance states organize opposing multicellular architectures in the aging brain

Genome maintenance is usually treated as cell-intrinsic, yet brain cells age within multicellular neighborhoods. Whether a cell's DNA damage response (DDR) state is systematically embedded in native tissue architecture is unknown. We used MERFISH to map curated repair programs across 604,252 cells in matched sections from 2-3 and 22-month-old mice. Regional DDR expression and coordination formed an age-dependent mosaic, accompanied by immune and oligodendroglial shifts. Independent metacell and distance-resolved analyses identified a consistent anchor-dependent organization. Low-DDR neurons occupied immune- and OPC-oligodendroglial-rich niches. In contrast, DDR-high vascular anchors were associated with vascular-cell enrichment and, in cortex and cerebral nuclei, OPC-oligodendroglial enrichment, whereas immune cells were enriched around DDR-low vascular anchors. Thus, genome-maintenance state was associated with distinct anchor-cell-specific spatial context depending on anchor-cell identity and its DDR transcriptional state. These opposing neuronal and vascular patterns define anchor-dependent genome-maintenance niches as a spatial feature of brain aging, with implications for regional vulnerability.

neuroscience↗

bioRxiv2025

PD-1 regulates CD4+ T cell-mediated CD8+ T cell responses in the brain to balance viral control and neuroinflammation

Programmed cell death protein 1 (PD-1) is expressed by T cells during progressive multifocal leukoencephalopathy (PML), a life-threatening brain disease caused by the human-only JC polyomavirus. Why PD-1 blockade finds variable success in PML patients is unclear. Brain CD4+ and CD8+ T cells are PD-1high during mouse polyomavirus (MuPyV) encephalitis. Here, we show that PD-1 loss during MuPyV infection acts in a brain-autonomous manner to increase the magnitude of brain-infiltrating CD4+ and CD8+ T cells and the function of virus-specific CD8+ T cells; in concert, brain virus levels decline and neuroinflammation increases. Deletion of PD-1 in CD4+ T cells, but not CD8+ T cells, recapitulates effects of global PD-1 loss. Single-cell RNA sequencing shows that PD-1-deficient CD8+ T cells cluster as effectors while transcripts associated with proliferation and function are upregulated with loss of PD-1. Thus, CD4+ T cell-intrinsic PD-1 signaling balances antiviral defense against neural injury during polyomavirus CNS infection.

immunology↗

bioRxiv2023

An altered cell type-specific subcellular distribution of translesion synthesis DNA polymerase kappa (PolK) in aging neurons

Genomic stability is critical for cellular function, however, in the central nervous system highly metabolically active differentiated neurons are challenged to maintain their genome over the organismal lifespan without replication. DNA damage in neurons increases with chronological age and accelerates in neurodegenerative disorders, resulting in cellular and systemic dysregulation. Distinct DNA damage response strategies have evolved with a host of polymerases. The Y-family translesion synthesis (TLS) polymerases are well known for bypassing and repairing damaged DNA in dividing cells. However, their expression, dynamics, and role if any, in enduring postmitotic differentiated neurons of the brain are completely unknown. We show through systematic longitudinal studies for the first time that DNA polymerase kappa (POLK), a member of the Y-family polymerases, is highly expressed in neurons. With chronological age, there is a progressive and significant reduction of nuclear POLK with a concomitant accumulation in the cytoplasm that is predictive of brain tissue age. The reduction of nuclear POLK in old brains is congruent with an increase in DNA damage markers. The nuclear POLK colocalizes with damaged sites and DNA repair proteins. The cytoplasmic POLK accumulates with stress granules and endo/lysosomal markers. Nuclear POLK expression is significantly higher in GABAergic interneurons compared to excitatory pyramidal neurons and lowest in non-neurons, possibly reflective of the inherent biological differences such as firing rates and neuronal activity. Interneurons associated with microglia have significantly higher levels of cytoplasmic POLK in old age. Finally, we show that neuronal activity itself can lead to an increase in nuclear POLK levels and a reduction of the cytoplasmic fraction. Our findings open a new avenue in understanding how different classes of postmitotic neurons deploy TLS polymerase(s) to maintain their genomic integrity over time, which will help design strategies for longevity, healthspan, and prevention of neurodegeneration.

neuroscience↗

bioRxiv2020

Epitope-Based Peptide Vaccine against Bombali Ebolavirus Viral Protein 40: An Immunoinformatics Combined with Molecular Docking Studies

BackgroundBombali Ebolavirus is RNA viruses belong to the Filoviridae family. They are causing lethal hemorrhagic fever with high mortality rate. Despite having available molecular knowledge of this virus, no approved vaccine or antiviral drugs have been developed yet for the eradication of Bombali Ebolavirus infections in humans. Objectivethe present study described a multi epitope-based peptide vaccine against Bombali Ebolavirus matrix protein VP40, using several immunoinformatics tools. Materials and MethodsThe six strains of Ebolavirus were retrieved from NCBI and Uniprot databases and submitted to VaxiJen to identify the most antigenic protein among all. Then PSIPRED, SOPMA, QMEAN, and PROCHECK tools were used to check the protein quality. T-cell prediction, population coverage, and molecular docking analysis were achieved to select peptides containing multiple Bombali VP40 epitopes showing interaction with multiple HLA molecules for expected immune response across the world. ResultBombali Ebola (YP_009513276.1) was found to be the most antigenic protein among all. Which it has been used in all required analysis. For T cell three epitopes showed high affinity to MHC class I (YSFDSTTAA, VQLPQYFTF, and MVNVISGPK) and high population coverage against Africa and the world. Furthermore in MHC class II, six promising epitopes that associated with most common MHC class II alleles. ConclusionThe above result conclude that, these peptides capable of provoking T-cell response and being interacted with a wide range of HLA molecules have a strong potential to be a vaccine against Bombali Ebolavirus.

bioinformatics↗