Molecular Foundations of Neuropharmacology

1
Molecular Foundations of Neuropharmacology

• Chapter 3

2
First Thoughts

• A lot of new material beyond Behavioural
  Neuroscience last week bio, this week more
  chemistry
• Need to understand
• Genetics
• How neuropharmacologists isolate and sequence new
  peptides, proteins, receptors etc
• Cloning
• Molecular basis of NT release and response

3
What can molecular biology do for us?

• Define atomic structure of critical molecules
• Define drug molecular makeup and which molecules
  it interacts with in the brain
• Used to only be able to study actions

4
Basics

• Most drug receptors involve sites with
  neurotransmitters act
• May also act by regulating intracellular enzymes
  that interact with NT processes
• End result is usually a change in membrane
  properties or intracellular metabolism, then
  cells and systems

5
Basics Continued

• Problem of unknown molecules
• Watson and Crick
• Gene manipulation gene products
• Cloning, sequencing, and engineering
• PCR and transgenic animals

6
Cellular variations

• Genome
• Genotype vs phenotype
• Stages of gene expression
• Transcription
• mRNA
• Protein synthesis and integration
• ER - secretion

7
Molecular Interactions

• DNA complementarity
• ATGC
• Code
• Gene segments

8
Interactions Continued

• How are DNA sequences determined
• Fast cloning once-over
• Polymerase chain reaction

9
Strategies in Neuropharmacology

• Short cuts in isolation and sequence
  determination
• Antisense oligonucleotides
• Null cells

10
Clone Screening and Selection

• Enrichment
• Recognition
• Building relevant DNA
• What if you dont know general seach

11
Beyond Clones

• Antisera, low-res to high-res maps, and
  multigenetic desease determination

12
Molecular aspects of NT release and response

• Na channels
• Ca2 channels
• K channels
• Receptors
• NT transporters

13
Molecular aspects of NT release and response
continued

• Synaptic vesicle proteins
• Synapsins, synaptotagmin, synaptobrevin, and
  synaptophysin
• SNAP-25 and syntaxin
• NSF

14
Summary

• Great gains in molecular biology
• Know the limits of what we can do
• Be able to describe how the genetic underpinnings
  of a given protein can be identified and
  manipulated

15
Next Week

• Chapter 4 Receptors