2026-10-11T01:37:38Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33946156 2026-09-30T00:15:04Z category_24739 portal_12 item_type_5 month_year_09_2026

Sonalani Shandil: Microglial phenotypes in Amyotrophic Lateral Sclerosis linked to C9orf72, SOD1, or UBQLN2 genetic variants Sonalani Shandil (8529651) Neurology and neuromuscular diseases Neuroscience MND ALS Microglia Neuron StemCell Neuroinflammation Neurodegeneration <p dir="ltr">Background: ALS incidence in Aotearoa is among the highest globally. While ALS involves neuronal degeneration, microglia are recognised disease propagators, though whether different ALS-causing variants converge on a shared neuroinflammatory pathway or drive distinct microglial phenotypes remains unknown.Objectives: To determine how three ALS-causing variants alter homeostasis and inflammatory responses in iPSC-derived microglia.Methods: iPSC-microglia carrying C9orf72 HRE, SOD1A4V, or UBQLN2P506T variants (n=1 line/genotype), or isogenic controls, were stimulated with LPS/IFNγ (100 ng/mL) for 8 or 24 h. Immunofluorescence imaging quantified immunophenotype markers.Results: SOD1A4V microglia matched control immunophenotype, showing expected activation/chemokine marker upregulation. C9orf72 HRE microglia appeared constitutively primed, with elevated baseline C1q, IL-6, and delayed chemokine upregulation. UBQLN2P506T microglia initially responded but showed progressive loss of inflammatory signaling, with IL-6 and HLA-DR declining by 8 h and markedly reduced by 24 h.Discussion: ALS-associated microglial dysfunction appears genotype-dependent, with SOD1A4V retaining near-normal reactivity while C9orf72 HRE microglia show distinct, mutation-specific aberrant phenotypes.</p> 2026-09-30T00:15:04Z Image Poster 10.17608/k6.auckland.33946156.v2 https://figshare.com/articles/poster/Microglial_phenotypes_in_Amyotrophic_Lateral_Sclerosis_linked_to_C9orf72_SOD1_or_UBQLN2_genetic_variants/33946156 CC BY 4.0