NEUROPROTECTIVE AND NEUROPRESERVATIVE EFFECTS OF NUTRACEUTICALS IN NEURONAL CULTURES: POTENTIAL PREVENTIVE AND THERAPEUTIC STRATEGIES IN ALZHEIMER’S DISEASE (AD)
Debomoy K. Lahiri and Balmiki Ray
Laboratory of Molecular Neurogenetics, Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, 791 Union Drive. Indianapolis, Indiana, USA
Alzheimer’s disease (AD) accounts for the largest proportion of dementia cases in the elderly, and while five FDA-approved drugs for AD demonstrate significant improvements in cognition and global assessments, none cure the disease. Thus, new therapeutic strategies must be devised. Deposition of amyloid β (Aβ) peptides in the brain interstitial spaces followed by severe neuroinflammation is one of the key features of AD. Deposited Aβ can activate microglia, which in turn initiates inflammatory responses leading neuronal loss. Since AD has a complex and diverse etiopathogenesis, drugs interfering with a specific pathway of the disease pathology may not be suitable therapeutic candidates. This is reflected in the recent failures of several drugs in clinical trials. We hypothesize that drugs with pleiotropic properties, i.e. ability to modify several pathological cascades, can be potential preventive and/or therapeutic candidates for AD. In recent past, we have observed remarkable neuroprotective and neuropreservative properties of certain nutraceuticals both in neuronal culture and in vivo. Our interest to test synthesizable pure nutraceutical agents in AD models is based on the following fact: A large epidemiological study had depicted significant (~4.4-fold) less incidence of AD in Indian elderly when compared with a reference American populace (Chandra et al, 2001). This finding indicates a strong environmental contribution in the development of AD, which may include dietary factors. We have observed that S-allyl-L-cysteine (SAC), an ingredient of garlic can preserve neurons from oxidative insults. SAC treatment in transgenic mice leads to preservation of pre-synaptic protein synaptophysin, which was observed significantly deficient in AD brain (Ray et al., 2011a). In other studies, curcumin, a polyphenol found in turmeric root was found to preserve pre-synaptic protein SNAP25 in neuronal cells. We recently demonstrated that a nanoformulation of curcumin (NanoCurc™) has greater bioavailability than that of free curcumin and intra peritoneal administration of NanoCurc™ in mice resulted in robust brain concentrations of curcumin (Ray et al, 2011b). We have also observed neuropreservatory properties of SAC, N-acetyl cysteine (NAC) and nanocurcumin in primary human fetal neuron cultures. Taken together, specific compounds obtained from several nutrients have displayed beneficial roles in preserving and protecting neurons from degeneration and can have potential therapeutic efficacy in AD. These results would accelerate further studies with these compounds in larger pre-clinical and clinical settings.