NEUROPROTECTION

Overview of Neurodegenerative Diseases

Recent advances in understanding the biological processes of neuronal cell death as well as improved methods for demonstrating therapeutic effects in humans has led to the concept of pharmacological neurocytoprotection. Accordingly,  the search for drugs with a neuroprotective effect  has  now became an  active trend for neuronal diseases such as Parkinson's disease (PD),  Alzheimer's disease (AD),  Huntington's disease, amyotrophic lateral sclerosis or even multiple sclerosis. The two most common and classical examples of neurodegenerative diseases, AD and PD, are used here to highlight the scientific merits of our project.

AD is the most common form of senile dementia affecting millions of people worldwide (Alzheimer's Society). The neuropathological hallmarks of AD include excessive accumulation of abnormal tau filaments in neurofibrillary tangles, abundant deposits of β-amyloid in senile plaques, and extensive neuronal degeneration. Although the cause of the neuronal degeneration in AD is not known, recent studies revealed a possible link between neuronal apoptic cell death and increased β-amyloid production.  It has further been shown that oxidative stress is linked to β-amyloid-mediated neuronal cytotoxicity as it triggers and/or facilitates neurodegeneration through a wide range of molecular events which eventually lead to neuronal cell loss. Interestingly, antioxidants have recently been shown to  have a beneficial effect in neurodegenerative disorders, β-amyloid-induced neurotoxicity and oxidative stress in neuronal cells. Antioxidants may thus emerge as one of the therapeutic strategies to treat β-amyloid-induced neurotoxicity and improve neurological outcome in AD.

PD is a further example of typical neurodegenerative disorder and is characterised by symptoms including rest tremors, postural instability, gait abnormality, bradykinesia and rigidity (see Parkinson's Disease Society). The major pathological change of Parkinson's disease is the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. The nigral vulnerability fits well with the strong oxidative stress observed in PD. Excessive reactive oxygen species generation that is caused by increased oxidative damage and reduced antioxidant level has been identified within the degenerating substantia nigra of PD patients.  Interestingly, neurotoxins to dopaminergic neurons such as 6-hydroxydopamine (6-OHDA) which are routinely used to induce experimental Parkinsonism are known to induce the formation of free radicals, inflammatory processes and apoptosis. The toxicity of such Parkinson-inducing agents can also be altered by antioxidants.

Our Research Strategy

We  have already developed and used several in-house bioassay screens for the identification of  natural antioxidants. Our natural products have been demonstrated to possess potent protective effects against oxidative damage to biological molecules including DNA, as well as cytoprotection in a variety of experimental conditions [see under publication]. We are now further  studying the effect of our  natural antioxidant medicinal plants and their metabolites through  in vitro models of AD and PD. Our procedures utilise tissue culture-based  neurotoxicity/neuroprotective studies with biochemical endpoint measurements using   colourimetric, flouresence, flow cytometeric  and electrophoresis analysis.

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