C7 Flashcards
Explain protein & diseases
- Arise due abnormal protein
- Can be diagnose or treated at DNA, RNA or proteins levels
- At each stage, disease related protein can potentially act as biomarker & therapeutic target
Various role of protein & their potential for manipulation such as
- Initiation of diseases
- Development of diseases
- Outcome of disease
Explain cystic fibrosis
- caused by changes in ion channel
- Unable to regulate Cl ion movement
- Cause thick, sticky mucous that affect lungs
- cause bone problem & mobility
Symptoms of cystic fibrosis
- Bad cough
- Repeat chest infection
- Diarrhoea
- Poor weight gain
Explain cystic fibrosis gene
- 3 bp deletion that lead to Del580
- 27 exon
- CFTR: 1440 amino acid
- 2 ATP binding cassettes
Effects of Cl- ion movement
- Na constantly pump out of cell
- Flow of Cl out of cell provide counter ion effect
- Allow graduent of NaCl to build up
- Water move from blood vessel to epithelial in response to NaCl gradient
What happen to ion movement if CFTR gene defective
- Water movement inhibited
- Produce thick mucus
- Effect lungs
Example of drug for cystic fibrosis
- Genistein
- Phenylbutyrate
- Osmolites
Explain protein misfolding disease
- Not involve changes in genome
- Group of diseases share the same pathophysiology
- Arise from normal protein in body that undergo changes in shapes
Example of protein misfolding disease
- Transmissible spongiform encephalopathies (TSE)
- Alzheimer
- Parkinson
- Type 2 diabetes
Pathophysiology of protein misfolding disease
- Abnormal protein
- Aggregates
- Froms amyloids
- Plague
- Holes
- Sponge
- Death
Explain TSE
- Involve formation of plaque & holes in brain
- Loss of control, dementia & death
- Cause by prions (proteninaceous infectious agent)
Types of TSE
- Scarpie: sheep
- BSE & Mad cow: cow
- Kuru & CJD: Human
- CJD, GSS & Fatal Familial insomnia: Familial
Explain prion
- Named as PrP (prion protein)
- Size in 27-30 kDa
- Found in normal cells
Difference between PrPc & PrPSc
PrPc
- Normal prion
- On surface of neurons
- Bind to Cu ions
- Digested by proteinase K
PrPSc
- Abnormal prion
- Aggregate to form structure amyloid fibres
- Accumulate to from plaque
- Protease resistant
How PrPSc convert all PrPc to abnormal
- Infection with PrPSc convert normal PrP from contaminated brain products or surgery tools
- PrPSc resistant to autoclave
- Denature PrPSc can renature
Explain Alzheimer disease
- Cause by abnormalities of amyloid beta & Tau protein
- Coded by APP gene
- Crucial for neuron growth, survival & repair
Mechanism of Alzheimer disease
- APP cut into smaller amyloid beta peptide which form amyloid plaques
- Tau become hyperphosphorylated which aggregate to lead to brain shrinkage
Explain parkinson disease
- Protein a-synuclein - unknwon function
- Exist as membrane bound a helices in cytoplasm
- Change shape to b sheet like oligomer & aggregate into fibrils and to Lewis bodies
Explain type 2 diabetes
- Amylin - islet amyloid polypeptide
- Produce by beta cell in pancreas
- Hormone that acts in glycemic control (role of insulin)
- Aggregate into fibrils & kill beta cell
- Cause diabetes
Possible therapy for protein misfolding disease
- Re-chaperoning
- Use small molecule to stabilise protein in correct form
Diseases development occur due to
- Accumulation of abnormal protein
- Action of subsequent abnormal protein
Action of subsequent abnormal protein include
- Cell escape from original sites
- Protection against immune system
- Mediating metastasis
Example of abnormal expression
MUC1 in breast cancer
- Glycoprotein of MUC1 abnormally expresedd
- Normally, cell adhere to each other & line on basal membrane
- Charged glycan on MUC1 form protective shield for the cell
- Abnormal will prevent cell adherence, charge glycan MUC1 repel each other & escape to metastasis
Her-2/neu In breast cancer
- Is a growth factor receptor that bind to growth factor to start cell proliferation
- Breast cancer cell over expressed to bind with excess growth factor
- Cause hyper proliferation & metastasis
