Title:Novel Target Sites for Drug Screening: A Special Reference to Cancer, Rheumatoid Arthritis and Parkinson’s Disease
Volume: 14
Issue: 2
Author(s): Neeraj Kumar*, Anita Singh, Dinesh Kumar Sharma and Kamal Kishore
Affiliation:
- Dr. Ram Manohar Lohiya Institute of Pharmacy, Kunwarpur Badagaon, Powayan, Shahjahanpur, UP,India
Keywords:
Cancer, Parkinson's disease, rheumatoid arthritis, novel target, Signal transduction, dopaminergic neurons.
Abstract:
Background: The humans can be affected by more than 100 types of cancers in which
about 22 % cancer death are caused by tobacco, 10% due to alcohol and obesity, 5-10 % by genetic
defects and 20 % by infections. Rheumatoid arthritis, an autoimmune disorder, occurs
mostly in middle age, affects 2.5 times more to females than males and till 2015, more than 24.5
Million people get affected from this disorder. The deaths due to rheumatoid arthritis were 28000
in 1990 and increased to 38000 in 2013. Parkinson’s disease, a neurodegenerative disorder of central
nervous system affects about 6.2 million people in 2015 and responsible for approximately
117400 deaths worldwide. Parkinson’s disease occurs mainly over the age of 60 and males get
more affected than females.
Methods: Bibliographic database has created by mendeley desktop software for available literature
in peer reviewed research articles especially by titles and disease names as keywords with
AND Boolean operator (title AND year or author AND year). The intervention and findings of
quality papers were extracted by detailed study and a conceptual framework has developed.
Results: Total 121 research and review articles are cited in this review to produce high impact in
literature for pathophysiology and receptors involved in all three diseases. Changes in enzyme action,
prohibition of angiogenesis and inhibition of microtubule are the main areas where anticancer
molecules may perform significant effect. The immune system is not a good target for rheumatic
treatment due to many complications that occur in body but fibroblast, like synoviocytes,
proteases which are responsible for cartilage destruction and osteoclast differentiation may be the
beneficial targets for pharmacoactive molecules in the treatment of rheumatoid arthritis. In Parkinson’s
disease, supply of dopamine to brain from outside results in brain dopamine synthesis decrement
which increase drug dependency. The compounds which stimulate secretion, reuptake inhibitor
and increment in dopaminergic neurons may be good targets.
Conclusion: Alteration of signal transduction by a drug is the goal of chemogenomics, a new
branch formed by combination of chemistry and genomics. The proliferation, angiogenesis and
apoptosis of cancer cells are regulated by cellular signaling of transcription factors, protein
kinases, transmembrane receptors, extracellular ligands and some external factors like oncogenic
mutations, ubiquitin-proteasome pathway with epigenetic changes. Traditional anticancer drugs
either alter DNA synthesis or control cell division while new drugs retard tumor growth or induce
apoptosis. The deterioration of dopaminergic neurons in substantia nigra results in Parkinson’s
disease with mental confusion, cognitive dysfunction and sleep disorder. Rheumatoid arthritis is
characterized by inflammation, autoimmunity, joint destruction, deformity and premature mortality
and treated mainly by anti-inflammatory and antirheumatic drugs. This review provides a
comprehensive summary of objects which may act as potential targets for many health disorders.