THE DEGENERATING BRAIN: MECHANISMS TO THERAPY

by Professor V Ravindranath, FNA, Centre for Neuroscience, Indian Institute of Science, Bangalore

Brain related disorders contribute up to one-third of the total disease burden in both developed and developing countries. Among the brain related disorders, which comprise both neurological and psychiatric illnesses, a cause of serious concern are the age-related disorders such as senile dementia including Alzheimer’s disease (AD) and Parkinson’s disease (PD) etc.

These disorders are progressive and irreversible and the etiopathogenesis of these disorders are poorly understood. They are characterized by loss of specific cells within certain regions of the brain leading to selective loss of function.

Our research focuses on understanding the molecular mechanisms underlying the selective cell death with a view to identify targets that can be used for disease modifying therapy and also identify such molecules from the knowledge base of traditional medicine. PD is a progressive movement disorder that results primarily from the death of dopaminergic neurons in the substantia nigra (SNpc). We have identified redox driven activation of cell-specific death signaling pathways and downregulation of cell survival pathways that contribute to the pathogenesis of Parkinson’s disease and explains the failure of drug that went into clinical trials.

Traditional systems of medicine, such as Ayurveda offer a knowledge base that can be utilized for development of therapeutic intervention strategies for treatment of these disorders. Using the knowledge base from Ayurveda, we have identified a herbal extract that reverses AD pathology. The remarkable therapeutic effect of the extract is mediated through up-regulation of low-density lipoprotein receptor-related protein (LRP) in the liver indicating that targeting the periphery offers a novel mechanism for rapid elimination of amyloid peptide for reversing the behavioral deficits and pathology seen in Alzheimer’s disease.

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