Cell signalling process
Any disease causing disruption along this pathway can cause damage
- disease happens when a cell response does not happen
Things that can go wrong - LIGAND
- not enough
- too much
- doesn’t degrade/uptake when it should
- pathogenic (e.g a virus)
Things that could go wrong - RECEPTOR
- too many expressed
- too few expressed
- stop responding to correct ligand
- respond to the wrong ligand
Things that could go wrong - INTRACELLULAR PATHWAY
- proteins don’t activate
- proteins don’t enter nucleus
- no transcription/ translation
- wrong transcription/translation
Examples of cell signalling disruption and disease
- metabolic disorders
- cancer
- neurodegenerative diseases
(Mention one of these in an exam question)
What is diabetes and what does it do?
- increases blood sugar
- damages tissues and organs
(Usually when there is blood sugar increase insulin is released which causes us to store more away)
Features of type 1 diabetes
- destroyed/impaired B cells of pancreas
- no insulin produced
- inherited
Features of type 2 diabetes
receptors become insensitive to insulin
Two pathways of insulin after binding to receptor
- binds to receptor
- receptor dimerises and cross phosphorylates
- this activates two pathways:
- PI3K—> GLUT4 channel opens
- Ras pathways —-> transcription
(If insulin didn’t bind to receptor the GLUT4 vesicle would not move to the membrane - no glucose uptake)
Stroke and glutamate excitotoxicity
- ischemic stroke (something goes wrong with the blood vessels and blood doesn’t get through to the cells which means oxygen doesn’t got through to the cells)
- the lack of oxygen means the oxygen can’t make enough ATP (lack of oxygen - decreased ATP)
- with out ATP there wont be enough activation of different pathways
- this causes a change in the membrane potential
- thus the voltage change will open VG receptors when it souldn’t
- Ca+ channels open
- Ca+ signals to release glutamate
- excess glutamate released from the cell
- this also causes decreased glutamate uptake
- glutamate is cytotoxic
- this leads to cytotoxicity, including to the neighbouring cells
This is how neurons die in stroke.
(Usually glutamate will be released in the correct amount into the cleft where the correct amount will bind to receptors - the wrong amount causes problems)
Cancer - how it occurs and progresses - errors in cell signalling
- occurs as a result of DNA damage or replication errors what can lead to:
- tumor suppressor genes becoming inactive
- improper formation of proteins
Proliferation - hyperactivation of pathways (cells dividing too much)
- PI3K-Akt and Ras-ERK pathways
- Myc: transcription factor that inappropriately amplifies
genes when hyperactivated
- this results in a clump of cells - tumor
Migration
- cell sometimes breaks away from its usual environment, this would usually trigger apoptosis
- apoptosis prevents unwanted cell survival
- if disables, cells can migrate and grow in incorrect areas
Alzheimers
Things that go wrong in alzheimers brain:
- tangles (tau proteins) and plaques (Bamyloid)
- over production of tau protein which gets tangled up in neuron and starts to destroy it (tau protein usually just regulates microtubules)
- plaques are when we have over production of Bamyloid forming clumps of proteins we dont want
- GSK3 also hyperphorpsrylates tau
JAK-STAT pathway
- found all over the body and does lots of things
Dysregulation of JAK-STAT is linked to:
- cancer
- rheumatoid arthritis
- IBS
- cardiovascular disease
- psoriasis
Viruses and cell signalling - COVID-19
- ACE2 is a receptor that regulates angiotension 2 (increases BP and inflammation) (keeping it high too much puts too much pressure on your heart and blood vessel)
- COVID-19 binds ACE2 and uses it to endocytose into cell
- this inhibits ACE2 action and thus angiotensin production increases
- angiotensin 2 is able to increase BP and inflammation is unchecked (increasing inflammation)
- this effects lungs, blood vessels, heart, kidneys, liver, GI tract
Only really need to know one of these pathways really well
Previous slides
How do therapeutic treatments utilize cell signlailling?
You can create a drug to activate or black a receptor
- cause or inhibit a cellular response
How do asthma inhalers work?
Reliever
- B2 adrenergic receptor agonist
- relaxes muscle in airways
Preventer
- corticosteroid (can travel across membrane of cell and find receptor)
- reduces inflammation
What is serotonin?
A neurotransmitter that controls mood
How do selective serotonin reuptake inhibitors (SSRIs) work?
- setatonin is a neurotransmitter that controls mood
- usually reuptake happens quickly after release form pre-synaptic neuron
- SSRIs inhibit reuptake
- more serotonin available to activate receptors on post-synaptic neuron
What does Imodium treat?
- diarrhea
How does Imodium work?
- treats diarrhoea
- activates opioid receptor in gut
- slows peristalsis
- increases water absorbtion
What is Imodium?
- leperamide
How does paracetamol work?
- inhibits enzymes COX1&2 that produce prostaglandins
- prostaglandins involved in inflammation
- its metabolite is an antagonist of TRPV1 receptor
- TRPV1 is involved in pain response
What to know form this module
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Lecture 10
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Lecture 20
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Lecture 30
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Lecture 40
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Lecture 50
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Lecture 60
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Lecture 741
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Lecture 824
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Lecture 968
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Lecture 1055
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Lecture 1266
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Lecture 1338
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Lecture 1448
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Lecture 1174
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Labs8
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Lecture 1269
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Lecture 1364
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Lecture 1456
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Lecture 1581
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16107
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1758
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1855
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1984
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2077
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2160
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2235
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