Research Mentor Name

Ryan Insolera

Research Mentor Email Address

rinsolera@wayne.edu

Institution / Department

Ophthalmology, Visual and Anatomical Sciences

Document Type

Research Abstract

Research Type

basicbio

Level of Research

no

Abstract

Determining Immune Activation in a Drosophila Model of ALS

Abrielle Fretz and Ryan Insolera

Background:

ALS is a progressive neurodegenerative disease that leads to muscle weakness and death. While most cases of ALS are sporadic, around 10% of cases are inherited. Of these inherited cases, one gene found to be involved is optineurin (OPTN). Mutated OPTN induces a cycle of cellular stress and death through NF-kB, a gene regulating immune activation and cell death. This dysregulation is thought to be a contributing factor to the disease processes of ALS.

In Drosophila, mutation of OPTN’s homologous gene, Kenny, was found to be involved in NF-kB-regulated immune system activation. Our lab has found that, similar to previous work on mammalian OPTN, the equivalent mutation to E478G in OPTN in the Kenny protein causes the protein to aggregate in fly neurons.

Methods:

Using the Gal4 system, we ubiquitously expressed E283G Kenny and extracted RNA from whole bodies of flies to assess systemic immune activation. We then compared the relative expression of anti-microbial peptides (AMPs), which represent the final downstream products of the fly immune system, between our wildtype, control, and mutant flies.

Results:

When looking at the AMPs Attacin C (attC), Diptericin B (diptB), and cecropin A1 (cecA1), we saw no significant change in mRNA expression between conditions. The lack of increase in AMP expression leads us to conclude that mutant Kenny expression does not activate the innate immune system as we previously hypothesized.

Conclusion:

These data may suggest that the pathogenic immune-activating effect of E238G Kenny may be tissue-specific, and therefore require a more focused investigation to fully understand the ALS disease process and cellular impact.

Disciplines

Biological Phenomena, Cell Phenomena, and Immunity | Medicine and Health Sciences | Nervous System Diseases

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