Happy
New Year! A lot happened in 2016, the staff and students here at SITraN have been working to
develop disease-modifying therapies for neurodegenerative diseases. There were numerous
papers published by SITraN researchers last year (too many to name them all),
so this is our yearly recap and summary of a select few…
Deficiency in the mRNA export
mediator Gle1 impairs Schwann cell development in the zebrafish embryo
A. Seytanoglu, N. I. Alsomali, C. F. Valori, A.
McGown, H. R. Kim, K. Ning, T. Ramesh, B. Sharrack, J. D. Wood, M. Azzouz.
Neuroscience 322 (2016) 287–297
Schwann cells are involved in protecting
neuronal axons which are responsible for carrying electrical impulses and
information between the body and the brain. They do this by wrapping themselves
around axons to produce what is called the myelin sheath; think of the plastic
jacket on a cable insulating the wires inside. Using a zebrafish model, the
authors found that these Schwann cells were not developing correctly in a nerve
when they knocked out a gene called GLE1,
which is affected in lethal congenital contracture syndrome 1 (LCCS1).
Zebrafish that had no Gle1 had less Schwann cells and therefore less insulation
around their nerves and this may be contributing to disease pathology and could
be an area of interest to focus research.
The C9orf72 protein interacts with Rab1a and the ULK1 complex to
regulate initiation of autophagy
C. P. Webster, E. F.
Smith, C. S. Bauer, A. Moller, G. M. Hautbergue, L. Ferraiuolo, M. A. Myszczynska,
A. Higginbottom, M. J. Walsh, A. J. Whitworth, B. K. Kaspar, K. Meyer, P. J.
Shaw, A. J. Grierson, K. J. De Vos
The EMBO Journal 35 (2016)
1597-1719
A mutation in the C9ORF72 gene is the leading cause of Amyotrophic
Lateral Sclerosis and Frontotemporal Dementia (C9ALS/FTD). The function of the
C9orf72 protein was, until recently, unknown. One of the proposed theories for
how the disease is caused is through reduced levels of the C9orf72 protein.
This paper from the De Vos group finds that C9orf72 interacts with another two
proteins called Rab1a and ULK1. Both these proteins are involved in a process
called autophagy, which is a mechanism used by cells to remove unwanted or
damaged parts. Further investigation found C9orf72 is specifically involved in
inducing autophagy and when C9orf72 was reduced in cells, autophagy decreased. Finally,
when they looked in neurons derived from C9ALS/FTD patients, autophagy appears
to be reduced in comparison to healthy controls.
http://emboj.embopress.org/content/35/15/1656.long
Evaluating a novel cervical
orthosis, the Sheffield Support Snood, in patients with amyotrophic lateral
sclerosis/motor neuron disease with neck weakness
S. Baxter, H. Reed, Z. Clarke, S. Judge, N.
Heron, A. McCarthy, J. Langley, A. Stanton, O. Wells, G. Squire, A. Quinn, M.
Strong, P. J. Shaw, C. J. McDermott.
Amyotrophic Lateral Sclerosis and
Frontotemporal Degeneration 17 (2016) 436-442
To counter the neck weakness suffered by ALS
patients, it is currently advised to wear a neck brace. Feedback from patients however
highlighted several issues they faced in doing so, such as their
restrictiveness. A project at SITraN was therefore set up to design a neck
brace (pictured) that allowed patients more flexibility whilst maintaining its
ability to support the neck. This paper from Dr Christopher McDermott’s team
describes the response from 26 ALS patients who evaluated the new neck brace.
The neck brace was received positively, with key beneficial features described
as: increased support while providing a greater range of movement, flexibility
of use, and improved appearance and comfort.
http://www.tandfonline.com/doi/full/10.3109/21678421.2016.1148170?scroll=top&needAccess=true
Oligodendrocytes contribute to motor neuron
death in ALS via SOD1-dependent mechanism
L. Ferraiuolo, K. Meyer, T.W. Sherwood, J.
Vick, S. Likhite, A. Frakes, C.J. Miranda, L. Braun, P.R. Heath, R. Pineda,
C.E. Beattie, P.J. Shaw, C.C. Askwith, D. McTigue, B.K. Kaspar.
PNAS 113 (2016) E6496-E6505
Oligodendrocytes
are cells that help to maintain the health of neurons in the brain and spinal
cord. Recent research suggests that oligodendrocytes play a role in ALS. To
discover how this happens, the authors of this paper turned cells from ALS
patients and healthy individuals into motor neurons and oligodendrocytes, and
grew them together in a dish. When ALS oligodendrocytes were grown with healthy
motor neurons, the neurons died. The
authors found that SOD1 (a protein known to behave abnormally in many ALS
patients) is likely to impair the ability of oligodendrocytes to properly
support motor neurons, causing the neurons to die. This research has provided
important insights into the toxic role of oligodendrocytes in ALS, which will
enable researchers to try and develop therapies to counteract these effects.
Gene expression profiling of the astrocyte
transcriptome in multiple sclerosis normal appearing white matter reveals a
neuroprotective role
R. Waller, M.N. Woodroof,
S.B. Wharton, P.G. Ince, S. Francese, P.R. Heath, A. Cudzich-Madry, R.H.
Thomas, N. Rounding, B. Sharrack, J.E. Simpson.
Journal of
Neuroimmunology 299 (2016) 139–146
In multiple sclerosis (MS),
myelin (an important insulating substance wrapped around axons) in the brain
and spinal cord becomes damaged. Areas
of the brain containing myelinated axons are known as “white matter”. In MS, white matter contains areas that are
demyelinated (lesions) and some normal-appearing white matter (NAWM), which is not
demyelinated. This paper aimed to
explore the role of astrocytes (supporting cells in the brain) in NAWM. Some evidence suggests that astrocytes are
protective in MS, but other research suggests that astrocytes might contribute
to lesion formation. To better
understand the role that astrocytes play in MS, the authors investigated which genes
are switched on or off in the NAWM astrocytes of MS patients. Genes
that were upregulated (more switched on) in MS patients compared to controls
were associated with supporting neuronal health and controlling responses to
oxidative and immune stresses, as well as regulating iron levels, suggesting
that NAWM astrocytes are protective in MS.
http://www.sciencedirect.com/science/article/pii/S0165572816302764
This blog was written by PhD students Katie Adamson and Yolanda Gibson.
Twitter: @katie_adamson_ @YolandaGibson_
Twitter: @katie_adamson_ @YolandaGibson_
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