A Natural Molecule Rescues the Memory and Locomotion Rhythmicity in Transgenic Drosophila of Alzheimer’s disease

The majority cases of Alzheimer’s disease (AD) are sporadic and age is the main risk factor for the disease. Therefore, ageassociated accumulation of oxidative damage on macromolecules can be the main cause of cellular demise. Brain is more sensitive to oxidative injury due to its higher rate of metabolism and lower capacity for regeneration. There are considerable evidences demonstrating deteriorated circadian rhythms and presence of oxidative damage in brain of AD patients. Takingthe advantage of UAS-GAL4 system in Drosophila, a transgenic model of AD expressing human tauR406W gene has beenconstructed to address the therapeutic potential of DHA I (4-hydroxy isophthalic acid), a novel natural molecule possessingstrong antioxidant profile derived from a medicinal herb Decalepis hamiltonii. Soxhlet sequential extraction was followed by RP-HPLC for obtaining 4-HIPA. Administration of the molecule to flies was achieved by mixing 0.1 mg/ml standard Drosophila culture media. Olfactory conditioning assay was conducted to measure the memory performance, locomotor activity was recorded under 12 h light/12 h dark at 25°C using Drosophila activity monitor (Trikinetics IV) and biochemical investigations were carried out to evaluate the activity level of antioxidant enzymes, catalase and SOD. Tau transgenic flies exhibited similar pathologic symptoms present in AD patients at the age of 30-day which was accompanied with decreased efficacy of antioxidant defense system. Chronic treatment of tau transgenic flies with 4-HIPA rescued their weakened cellular antioxidant defense system, cognitive deficit and circadian rhythmicity of locomotion behavior. 4-HIPA can be a suitable candidate for development of drugs targeting neurodegenerative disorders.

Keywords:

Drosophila , Alzheimer’s disease , Oxidative Stress , Circadian Rhythm , 4-HIPA