Making Connections

Professor Lawrence Steinman wins 2011 Charcot Award

Larry Steinman, winner of the 2011 MSIF Charcot Award Professor Lawrence Steinman, of the Stanford University School of Medicine, has been chosen to receive the MSIF's Charcot Award, a prestigious biennial award that recognizes a lifetime achievement in research into the understanding or treatment of multiple sclerosis (MS).

> Read more about Professor Steinman

Research News


	Summaries of all the latest research findings on MS selected by a team based at the Institute of Neurology, London.

Microglial cystatin F expression is a sensitive indicator for ongoing demyelination with concurrent remyelination

The authors examine the spatiotemporal expression pattern of cystatin F, a papain-like lysosomal cysteine proteinase inhibitor, by in situ hybridization and immunohistochemistry in animal models of demyelination and spinal cord tissue from multiple sclerosis (MS) patients. They demonstrate that the timing of cystatin F induction matches with ongoing demyelination, and cystatin F expression overlapped with the area where remyelination is taking place. Cystatin F induction was also found to stop in chronic demyelination, in which remyelinating ability was lost.

The authors suggest that their findings demonstrate that expression of cystatin F indicates ongoing demyelination/remyelination, and the absence of cystatin F expression indicates the cessation of remyelination in the demyelinating area.

authors: Ma J, Tanaka KF, Shimizu T, Bernard CC, Kakita A, Takahashi H, Pfeiffer SE, Ikenaka K.

source: J Neurosci Res. 2011 May;89(5):639-49

Decreased activity of the 20S proteasome in the brain white matter and gray matter of patients with multiple sclerosis.

The authors studied the degree of proteasomal dysfunction in MS in an attempt to understand the mechanisms behind the accumulation of oxidised proteins in the brains of patients with MS. They measured the activity of the 20S proteasome and other proteolytic systems in the cerebral white matter and grey matter of 13 MS patients and controls and found that the activity of three peptidases of the 20S proteasome system were reduced in the gray and white matter of patients with MS, although the amount of 20S proteasome present was not reduced. The authors suggest there may be a failure of 26S proteasome too, as proteins containing Lys-48 poly-ubiquitin were also found to accumulate in MS tissues.

The authors suggest that direct inactivation of proteolytic centers in the 20S particle and/or the presence of specific inhibitors is the underlying cause of proteasomal dysfunction in MS.

authors: Zheng J, Bizzozero OA.

source: J Neurochem. 2011 Apr;117(1):143-53

Complementary roles of grey matter MTR and T2 lesions in predicting progression in early PPMS

This large longitudinal imaging study which included 47 patients with PPMS evaluated the role of T2 lesion load (T2LL) and magnetisation transfer ratio (MTR) in the normal-appearing white matter (NAWM) and grey matter (GM) at study entry at predicting disease progression. The authors found that baseline T2LL and GM peak location and peak height MTR were independent predictors of progression, as measured by timed walk test, and that a greater progression rate correlated with a steeper increase in T2LL and a faster decline in GM mean and peak location MTR. The results suggest that there is a prognostic role to MRI in early PPMS.

authors: Tur C, Khaleeli Z, Ciccarelli O, Altmann DR, Cercignani M, Miller DH, Thompson AJ.

source: J Neurol Neurosurg Psychiatry. 2011 Apr;82(4):423-8.

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