Document Type

Abstract

Publication Date

2-11-2026

Academic Year

2025-2026

Comments

Presented at the 2026 Scholarly Inquiry (SI) Research Project Symposium.

Abstract

Amyotrophic lateral sclerosis (ALS) is a degenerative neuromuscular disease that progresses to respiratory paralysis and death. Defective protein homeostasis is a major driver of disease pathogenesis, and autophagy, a cellular recycling and degradation system, is often disrupted in disease. UBQLN2 mutation is linked to a small percentage of familial ALS. Despite UBQLN2’s known role in protein homeostasis, the effect of its ALS-associated mutation on neuronal autophagy remains unclear. This study used iPSC-derived excitatory cortical-like (iCN) and lower motor (iLMN) neurons to quantify the effects of the familial UBQLN2 mutation (P506T) on autophagic flux. Live cell imaging and ImageJ were used to count autophagosomes and autolysosomes using an automated approach to determine the proportion of acidified autophagosomes. Western Blot analysis of LC3-II, an autophagy marker, was also conducted to measure autophagosome relative levels, using Bafilomycin A1 to prevent autophagosome breakdown. Two-way ANOVA with 𝛼 = 0.05 was used to analyze the data. Live cell imaging analysis showed no significant difference in the number of autophagosomes or the proportion of acidified autophagosomes between wild type and mutant neurons for iCNs and iLMNs at 21- days post-induction. Similarly, Western Blot analysis showed no significant difference in LC3-II between wild type and mutant iCNs at 14- and 21-days post-induction. These findings suggest that UBQLN-2 mutation does not directly affect autophagic flux, either the rate of formation or degradation, in iPSC-derived neurons. Although the rate of autophagy is unchanged, future investigation will interrogate the effects of UBQLN2 mutation on neuronal autophagosome cargo selection and mitochondrial turnover.

Additional Files
Pilger_Marina_poster.pdf (4191 kB)

Language

English

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