Evaluation of Darunavir for Neuroprotective Activity in Alzheimer’s Disease

Y. Navya Reddy^a*, Nymisha Y^a, K. Rekha Rani^b, Kuruva Jyothirmai^b, R. Mohana Priya^c, R. Vadivelan^a, T. Spurthi^d
aDept. of Pharmacology, JSS College of Pharmacy, Udhagamandalam, Tamilnadu, India -643001
^bDept. of Pharmaceutics, CES College of Pharmacy, NH – 7, Chinnatekur, Kurnool, India – 518218.
^c Dept. of Pharmaceutical Chemistry, Dr. K .V Subbareddy Institute of Pharmacy, Kurnool, India – 518218.
^dDept. of Pharmacy Practice, CES College of Pharmacy, NH-7, Chinnatekur, Kurnool – 518218

A B S T R A C T
Alzheimer’s disease (AD) is associated by deposition of amyloid beta plaques due to improper processing of amyloid precursor protein and tau protein dephosphorylation ending up in formation of neuro fibrillary tangles. Gamma secretase belongs to aspartyl protease family sharing similarity in structure with HIV-Proteases, pepsin. Inhibition of this enzyme plays a key role in targeting this disease. Daurnavir is the drug currently employed in the treatment of HIV infections and its mechanism being the inhibitor of HIV proteases. HIV protease belongs to the Aspartyl protease (ASP) family and gamma secretase also being one of them. Since the test drug has high affinity towards that site, when reaches the brain can target the gamma secretase enzyme. Ab_(1-42) induction led to the development of dementia in experimental animals which was evident from the behavioral tests applied on the induced animals. After treatment with Low dose (60mg/kg, p.o) and high dose (120mg/kg, p.o) animals could recollect their memory and were successfully able to locate the reward and produced consistent results when compared with the negative control, indicating a positive note on drugs effect upon treatment. Histopathological reports showed that, upon treatment with the test gave better results with comparatively more neuronal density and uniformity clearly indicates that the test drug was able to fight the neurotoxicity and protect the brain from neurodegeneration. Results were consistent at higher dose level compared to low dose level group which showed a reasonable degree of degeneration and loss of uniformity in the distribution of neurons. Thus use of HIV proteases is a new targeting for AD.
Keywords: Alzheimer’s disease, Amyloid beta plaques, Gamma Secretase, HIV Protease, Darunavir