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.
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.
Gene expression profiling of the astrocyte transcriptome in multiple sclerosis normal appearing white matter reveals a neuroprotective role
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.
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