Abstract

PARKINSON’S DISEASE, ITS IMPLICATION AND TREATMENT WITH SPECIAL REFERENCE TO LIVER X RECEPTOR: A REVIEW

Rajnish Srivastava*, Deepa, Amit Kumar Srivastava, Piush Khare, Hemant Nagar,

ABSTRACT

Parkinson's disease is a chronic, degenerative neurological disorder that affects more than five million peoples worldwide. The risk of developing the disease increases with age. Sustained microglia over activation and resulting neuroinflammation is believed to play important role in the mechanism of chronic dopaminergic neuronal loss in Parkinson’s disease. The disease is characterized by skeletal muscle hypertonic and hyperkinetic impairment. The main objective for the effective treatment of Parkinson’s disease is to increase and replenish the dopaminergic activity of the brain. So, therapy consist use of drugs that either increase synaptic concentration of dopamine and dopamine release or inhibit its degradation. A new therapeutic target for the treatment of Parkinson’s disease has been identified. Liver X receptors (LXr-α, LXr-β) are ligand-dependent nuclear receptors which are targeted for ventral midbrain neurogenesis in vivo. Cholic acid and 24 (S), 25- epoxycholestrol (24-25 EC) are the two types where the latter was found to be the mostpotent in the developing mouse midbrain whereas both ligands promoted neural development in an LXr dependent manner in Zebrafish in vivo. Notably, each ligand selectively regulated the development of distinct midbrain neuronal populations. Whereas cholic acid has increases survival and neurogenesis of Brn3a positive red nucleus neurons, while 24-25 EC promoted dopaminergic neurogenesis. Moreover, 24-25 EC promoted dopaminergic differentiation of embryonic stem cells, suggesting that LXr ligands may contribute to the development of cell replacement and regenerative therapies for Parkinson's. Administration of the LXr agonist GW3965 to MPTP-treated wild type, mice protected against dopaminergic loss in neurons along with the fibers projecting to the striatum. Hence a novel strategy can be designedwherein the drug viz. dopamine can be loaded in brain targeted carrier system which is loaded or coupled to LXr ligand which will act in dual way for management of Parkinsonism

Keywords: Parkinson’s disease, Neuroinflammation, Neurogenesis, Microglia, LXr-?, LXr-?, Cholic acid and 24(S), 25-epoxycholestrol (24-25 EC)