<i>Drosophila</i> eye model to study the role of NAT9 in Alzheimer’s Disease related Dementia (ADRD)

Background One of the hallmarks Alzheimer’s disease (AD), an age-related progressive form dementia, is accumulation amyloid beta (Aβ42) plaque, which manifests in decline cognitive function. The these Aβ42 plaques trigger hyperphosphorylation tau, a microtubule associated protein, results intracellular neurofibrillary tangles (NFTs) due to destabilization microtubules. Method We employed Gal4/UAS system Drosophila melanogaster misexpress human within developing fly retina, exhibiting AD-like neuropathology. Accumulation plaque(s) triggers aberrant activation signaling pathways like JNK pathway resulting neuronal cell death by unknown mechanism(s). Using candidate based forward genetic screening, we identified N-acetyltransferase 9 (NAT9) as one modifiers GMR>Aβ42 reduced eye phenotype. Previously NAT9 has been shown stabilize microtubules acetylation tubulins, thereby inhibiting signaling. This study aims understand role Aβ42-mediated neurodegeneration. Result gain-of-function rescues neurodegeneration whereas loss-of-function enhances have also found that suppresses suggesting functional conservation. Interestingly, mutated acetyl- CoA binding site shows similar phenotype its function independent activity. Moreover, antennal imaginal discs background increased pJNK levels. Conclusion Our data suggests downregulates can ameliorate