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Drug target

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B-Tech.NIET..Introduction to Bio Science …

B-Tech.NIET..Introduction to Bio Science
By:-Sanchi Dua


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  • 1. DRUG TARGETS AND DRUG DESIGN Ms. Sanchi Dua M. Tech. Biotechnology (2009-11)
  • 2. Introduction: Alzheimer's Disease • Progressive Neurodegenerative Disorder • Acute Cognitive Decline Neuronal Cell Dysfunction Memory Loss Poorly understood
  • 3. Amyloid Beta (Aβ) Aβ (betaamyloid peptide) Hallmark of Alzheimer's disease (AD) Yeast Cells used to study harmful effects
  • 4. Pathological Characterization • Accumulation of extracellular beta amyloid (Aβ) plaques • Intracellular tau tangles • Gliosis • Neuronal cell death
  • 5. Research Objective Identify biomarkers • Peripheral Biomarkers • Blood samples easy to obtain Novel cognitive- • Increased Efficacy and Safety enhancing therapeutic strategies
  • 6. Existing clinical methods of diagnosis Brain Imaging Characterizing fluid biomarkers Cerebrospinal fluid (CSF)
  • 7. Blood-based biomarkers Potential sources Platelets Small, anuclear fragments derived from megakaryocytes in the bone marrow Platelets Respond to neurotransmitters Enzymes responsible for generating the Aβ peptide. High concentration of amyloid precursor protein (APP)
  • 8. Methodology for identifying Biomarkers Validation of Cooccurrence of other pooled analyte changes consistent with previous biomarker studies Platelet isolation and membrane protein enrichment Quantification of membrane-enriched proteome
  • 9. Cognitive Aging Aging Cognitive functions decline
  • 10. Current drug targets To improve cognitive function Inhibit acetylcholinesterase (AChE) N-methyl-D-aspartate receptor
  • 11. Novel cognitive-enhancing therapeutic strategies To slow disease progression in AD patients To enhance cognitive function
  • 12. Potential Drug Targets Metabotropic glutamate receptor subtype 5 • Increasing the activation of mGlu5 Nicotinic acetylcholine receptor • Activation of the α7nAChR subtype with smallmolecule agonists M1 Muscarinic acetylcholine receptors • potential to affect multiple disease pathologies including amyloid-beta and phosphorylated tau
  • 13. Potential Drug Targets • Indirect cholinergic 5Hydroxytryptamine stimulation through 5-hydroxytryptamine receptors (5-HT) receptors 6 Norepinephrine • Noradrenergic neurons: vulnerable during aging Cyclic adenosine monophosphate • cAMP signaling is increased with aging
  • 14. Experimental Techniques • Immunostaining • Immunoblot • Indirect ELISA Assay • Mass spectrometry (MS)-based proteomics