Using newly available genetic sequencing
scientists discovered cells infected with prions (the infectious
agent responsible for these diseases) release particles which
contain easily recognized 'signature genes'.
Effective diagnosis and treatment of
prion disease is hampered by the absence of effective ante-mortem
diagnostic methods. The identification of non-invasive, sensitive
and specific diagnostic markers during the pre-clinical phase is of
major importance.
Associate Professor Andrew Hill — from
the Department of Biochemistry and Molecular Biology at the Bio21
Institute — said these particles travel in the blood stream, making
a diagnostic blood test a possibility.
"This might provide a way to screen
people who have spent time in the UK, who currently face
restrictions on their ability to donate blood," he said.
"With a simple blood test nurses could
deem a prospective donor's blood as healthy, with the potential to
significantly boost critical blood stocks."
Mad Cow disease was linked to the deaths
of nearly 200 people in Great Britain who consumed meat from
infected animals in the late 1980s.
Since 2000, the Australia Red Cross
Blood Service has not accepted blood from anybody who lived in the
UK for more than six months between 1980 and 1996, or who received a
blood transfusion in the UK after 1980.
Prion diseases are transmissible
neurodegenerative disorders affecting both humans and animals. The
cellular prion protein, PrPC, and the abnormal infectious form,
PrPSc, are found associated with exosomes, which are small 50–130 nm
vesicles released from cells.
Exosomes also contain microRNAs (miRNAs), a class of non-coding RNA,
and have been utilized to identify miRNA signatures for diagnosis of
disease.
While some miRNAs are deregulated in prion-infected brain tissue,
the role of miRNA in circulating exosomes released during prion
disease is unknown. Here, researchers investigated the miRNA profile
in exosomes released from prion-infected neuronal cells.
They performed the first small RNA deep sequencing study of exosomes
and demonstrated that neuronal exosomes contain a diverse range of
RNA species including retroviral RNA repeat regions, messenger RNA
fragments, transfer RNA fragments, non-coding RNA, small nuclear
RNA, small nucleolar RNA, small cytoplasmic RNA, silencing RNA as
well as known and novel candidate miRNA. Significantly, we show that
exosomes released by prion-infected neuronal cells have increased
let-7b, let-7i, miR-128a, miR-21, miR-222, miR-29b, miR-342-3p and
miR-424 levels with decreased miR-146 a levels compared to
non-infected exosomes.
Overall, these results demonstrate that circulating exosomes
released during prion infection have a distinct miRNA signature that
can be utilized for diagnosis and understanding pathogenic
mechanisms in prion disease.
Lead author Dr Shayne Bellingham said
the breakthrough might also help detect other human
neurodegenerative diseases, such as Alzheimer's and Parkinson's.
The research was undertaken at the
University of Melbourne, with assistance from the Mental Health
Research Institute of Victoria, the National Health and Medical
Research Council and the Australian Research Council.
For more information
The research is published in the Oxford University Press Nucleic
Acids Research journal.
Small RNA deep sequencing reveals a distinct miRNA signature
released in exosomes from prion-infected neuronal cells.
Authors: Shayne A. Bellingham, Bradley M. Coleman and Andrew F.
Hill.
http://nar.oxfordjournals.org/content/early/2012/09/08/nar.gks832.full
University of
Melbourne
(MDN) | 
