Biology subjects

Montal, V.

Publications and source records attributed to Montal, V..

3 recordsLinked to original sources

bioRxiv2026

Site-Specific Entry Factors Define Cellular Susceptibility to SARS-CoV-2 in Human Tissues

SARS-CoV-2 primarily infects the respiratory epithelium through entry factors ACE2 and TMPRSS2. However, alternative viral entry receptors and/or modulators of viral entry factors expression may contribute to infection in respiratory as well as non-respiratory tissues, including the kidneys and colon. Using single-cell analyses, we identified novel candidates for spike-mediated viral entry in epithelial cells from diverse fresh human tissues exposed to a labeled spike-pseudotyped virus. Systematic viral tracking revealed tissue-specific membrane receptors that contribute to viral entry, functionally validated in human tissues and partially predicted by molecular modeling. We found ADAM17 and IL1R1, together with canonical molecules, to significantly facilitate viral entry in the lung parenchyma, while entry into the renal cortex was less dependable on canonical factors, but strongly modulated by JAK1/2 engagement. These findings uncover distinct viral entry mechanisms across tissues and suggest novel organ-specific therapeutic targets for patients at risk.

microbiology↗

bioRxiv2020

Characterization of the motor cortex transcriptome supports microgial-related key events in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the degeneration of upper and lower motor neurons. A major neuropathological finding in ALS is the coexistence of glial activation and aggregation of the phosphorylated transactive response DNA-binding protein 43-kDa (pTDP43) in the motor cortex at the earliest stages of the disease. Despite this, the transcriptional alterations associated with these pathological changes in this major vulnerable brain region have yet to be fully characterized. Here, we have performed massive RNA sequencing of the motor cortex of ALS (n=11) and healthy controls (HC; n=8). We report extensive RNA expression alterations at gene and isoform levels, characterized by the enrichment of neuroinflammatory and synapse related pathways. The assembly of gene co-expression modules confirmed the involvement of these two principal transcriptomic changes, and showed a strong negative correlation between them. Furthermore, cell-type deconvolution using human single-nucleus RNA sequencing data as reference demonstrated that microglial cells are overrepresented in ALS compared to HC. Importantly, we also show for the first time in the human ALS motor cortex, that microgliosis is mostly driven by the increased proportion of a microglial subpopulation characterized by gene markers overlapping with the recently described disease associated microglia (DAM). Using immunohistochemistry, we further evidenced that this microglial subpopulation is overrepresented in ALS and that variability in pTDP43 aggregation among patients negatively correlates with the proportion of microglial cells. In conclusion, we report that neuroinflammatory changes in ALS motor cortex are dominated by microglia which is concomitant with a reduced expression of postsynaptic transcripts, in which DAM might have a prominent role. Microgliosis therefore represents a promising avenue for therapeutic intervention in ALS.

neuroscience↗

bioRxiv2018

Agreement between 18F-Florbetapir PET imaging and cerebrospinal fluid Aβ1-42, Aβ1-40, tTau and pTau measured on the LUMIPULSE G fully automated platform

INTRODUCTIONThe development of fully automated immunoassay platforms has improved the technical reliability of cerebrospinal fluid (CSF) biomarkers for Alzheimers disease.\n\nMETHODSWe quantified A{beta}1-42, A{beta}1-40, tTau and pTau levels using the Lumipulse G System in 94 CSF samples from participants of the SPIN cohort with available 18F-Florbetapir imaging. Amyloid scans were assessed visually and through automated quantification. We determined the cutoffs of CSF biomarkers that optimized their agreement with 18F-Florbetapir PET and evaluated concordance between markers of the amyloid category.\n\nRESULTSA{beta}1-42, tTau and pTau (but not A{beta}1-40) and the ratios with A{beta}1-42 had good diagnostic agreement with 18F-Florbetapir PET. As a marker of amyloid pathology, the A{beta}1-42/A{beta}1-40 ratio had higher agreement and better correlation with amyloid PET than A{beta}1-42 alone.\n\nDISCUSSIONCSF biomarkers measured with the Lumipulse G System show good agreement with amyloid imaging. Combination of A{beta}1-42 with A{beta}1-40 increases the agreement between markers of amyloid pathology.

neuroscience↗