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| Kuru: the science and the sorcery - documentary |
Only a few decades ago a strange phenomenon was witnessed by westerners
in Papua New Guinea. They found that members from the local Fore tribe
expressed symptoms of a then unknown infectious disease. This disease was locally
called Kuru and was discovered to be a consequence of cannibalistic rituals,
where women and children ate the brain of deceased tribe members. The symptoms
involved exhaustive shaking of the body and uncontrollable laughter, to only
name a few. It was first assumed that this mysterious disease was a virus
infection, but further research showed no evidence of virus particles in these
patients. The discovery that a certain class of proteins were to blame for this
infectious disease came as a shock. These proteins were subsequently named
prions. A prion mainly arises in the central nervous system and is harmless in
its normal structure. However, when it misfolds it starts to accumulate into
aggregates and causes irreversible degeneration in the brain. An intriguing
aspect of prions is that they can infect and trigger other normal prion
proteins to misfold as well! Due to the nature of prion diseases, researchers
hypothesised that other neurodegenerative disorders, such as Alzheimer’s
disease, share the same underlying mechanism. These disorders also involve
proteins that accumulate and cause neurotoxicity. It remains unclear however if
these diseases share the transmissibility that characterise prion diseases, but if they do this observation could have a tremendous impact on how we
perceive the cause and treatment of these diseases.
Prions, short for
proteinaceous infectious particles, were discovered by the famous Stanley
Prusiner in 1982. He succeeded in finding the cause behind Kuru and was awarded
the Nobel Prize for it in 1997. First it was thought that a virus was the pathogen.
However, no nucleic acids[1]
were found when investigating the brains of deceased tribe members. The
outbreak of mad cow disease, also called ‘Bovine Spongiform Encephalopathy’, in
the United Kingdom resulted in an incredible rise in research on prions. Various
prion diseases manifest themselves in humans, but also in animals. During the
BSE crisis, it was feared that prion diseases were transmissible between humans
and animals.
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| http://www.vce.bioninja.com.au/aos-2-det |
The prion-protein
is located on the cell surface of cells in the brain and the rest of the
nervous system. When the prion-protein, which is normally rich in alfa-helices,
misfolds by the acquisition of beta-sheets (both are secondary structures
of a protein), it accumulates in the brain. This results in degeneration of the
brain and nervous system in general. Normally, misfolded proteins are cleared
by an internal cell-mechanism, which recognises and destroys them so they can
not do any harm to the cell. The prion protein on the contrary, through it’s
structural change from the normal protein, is insoluble. The effect of this is
resistance to these cell mechanisms and the prions can continue to wreak havoc
in these tissues.
A peculiar thing
about prions is that they have infectious properties, just like bacteria and
viruses. Prions can infect other normal prion proteins which results in these
proteins to misfold as well. In this way aggregation is propagated throughout
the nervous system, where it blocks normal functioning. Misfolding can occur
due to genetic mutations[2],
infection through contact with infected tissue or sporadic occurrence of
misfolding proteins.
The last couple of years, researchers started
to compare prion diseases with other neurodegenerative disorders, such as
Alzheimer’s disease, ALS (Amyotrophic Lateral Sclerosis) and Parkinson’s
disease among others. They were stunned by the striking similarities between
prion disorders and these neurodegenerative disorders. Firstly, the diseases
are manifesting in the brain and in the rest of the nervous system of patients.
Secondly, all these diseases involved the accumulation of a particular protein
resulting in aggregation and neurotoxicity. Finally, the age-related mechanism
was apparent in all classes of disorders. All have a late-onset in life and
could be due to a decreased capability of the cell to clear aggregates. As
people are getting older than ever before in the known history of mankind,
there has been a higher incidence in neurodegenerative disorders, which makes
it essential to study the underlying fundamental processes to get to a
treatment. Since the
prion-like-mechanism was hypothesised a lot of research was conducted.
Recently, a new prion disease was found called Multiple System Atrophy and
involves the same protein that underpins Parkinson’s disease. Other research
showed that growth hormone that was given to patients, spread prion diseases
but was also accompanied by amyloid aggregates. The evidence for a prion-like
mechanism becomes more apparent, but also a rising concern on transmissibility
of prion-like disorders. This indicates the urgent need for fundamental
research on the prion-like mechanism, to get closer to a treatment for these
devastating disorders.
Manon Molenaar, 2015-10-08
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