Prion disease: protein misfolding and spongiform encephalopathy
A prion is an infectious protein: an abnormally folded form of the prion protein makes normal prion protein change shape too, so the protein clumps and kills neurones.
Remember
Prion protein that has misfolded (taken on the wrong shape) makes normal prion protein misfold too, and the clumps kill neurones, leaving a brain that looks sponge-like after death, with little inflammation.
The normal prion protein (PrP) sits on the surface of neurones and at synapses, where neurones meet. Its exact job is not known.
In prion disease, a PrP molecule misfolds, changing into an abnormal form called PrPsc (the sc stands for scrapie, the sheep prion disease). This form acts as a template, making normal PrP copy the wrong shape. The change repeats in a chain reaction, so the misfolded protein spreads without genes of its own.
The misfolded protein clumps together (aggregates) and resists the enzymes that normally break proteins down. Neurones die and leave microscopic holes, so after death (post mortem) the brain looks sponge-like. That is why the disease is called spongiform encephalopathy: spongiform means sponge-like, and encephalopathy means a disease of the brain.
Because a prion is an infectious protein rather than a virus or bacterium, antibiotics and antivirals do nothing. Prion disease provokes little classical inflammation, so routine tests for infection or inflammation often come back normal. The disease can be sporadic (arising without a known cause) or inherited through a faulty gene (a mutation of the prion protein gene). It can also be acquired: variant Creutzfeldt-Jakob disease can follow eating beef from cattle that had bovine spongiform encephalopathy (BSE, mad cow disease).
Creutzfeldt-Jakob disease (CJD) is the most common human prion disease. Its typical picture is a rapidly progressive dementia, with memory impairment, personality change, loss of coordination (ataxia) and visual disturbance. There is no cure.
Key facts
- Normal protein
- PrP sits at synapses on neurones, and little is yet understood of its function.
- Abnormal form
- PrPsc is the misfolded form, where sc is for scrapie in sheep.
- Spread
- PrPsc acts as a template, so a normal PrP molecule it meets is made to misfold, and the misfolded protein multiplies without genes of its own.
- Not a virus
- A prion is an infectious protein, not a virus or bacteria, so antibiotics and antivirals do nothing.
- How it arises
- The disease can be sporadic (no known cause), inherited through a faulty gene, or acquired, as in variant CJD from beef from cattle with BSE.
- Typical picture
- CJD causes a rapidly progressive dementia with personality change, loss of coordination and visual disturbance.
Exam traps
- Multiple sclerosis, in which the immune system attacks myelin, is a different process from prion disease, where protein accumulation kills neurones directly.
- A virus does not cause prion disease, so antiviral drugs have no effect, because a prion is a protein without genes of its own, not a virus or bacteria.
- Prion disease has no bacterial cause, so antibiotics do nothing, and granulomas, groups of immune cells that form around some chronic bacterial infections such as tuberculosis, are not a feature of it.
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