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More MS news articles for January 2003

Expression ratios of the Bcl-2 family proteins and disease activity in multiple sclerosis

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12507784&dopt=Abstract

J Neuroimmunol 2003 Jan;134(1-2):158-65
Sharief MK, Matthews H, Noori MA.
Department of Neuroimmunology, Guy's, King's and St. Thomas' School of Medicine, Guy's Hospital, SE1 1UL, London, UK

There is emerging evidence that failure of apoptosis (programmed cell death) of potentially pathogenic T lymphocytes may be involved in the pathogenesis of multiple sclerosis (MS).

The commitment of T lymphocytes to die is partly regulated by the Bcl-2 family proteins, which act as a checkpoint upstream of mitochondrial dysfunction.

These proteins include the death antagonists Bcl-2 and Bcl-X(L), and death agonists Bax and Bad.

Recent studies suggest that altered expression of Bcl-2 family proteins in T lymphocytes is involved in promoting cellular resistance to apoptosis in patients with MS.

However, the relationship between these alterations in Bcl-2 proteins expression and clinical disease activity has not yet been evaluated.

In this study, we analyzed the expression ratios of pro- to anti-apoptosis Bcl-2 family proteins in patients with clinically active MS and compared results to corresponding ratios in patients with stable MS and relevant control groups.

We observed a significant reduction in the expression ratios of pro- to anti-apoptosis Bcl-2 members in peripheral lymphocytes from patients with active MS when compared to corresponding ratios in patients with stable MS or other controls.

This imbalance in the expression ratios of pro- and anti-apoptosis proteins was functionally active in reducing cellular susceptibility to apoptosis in active MS.

It also correlated with clinical features of disease activity, such as the number of gadolinium-enhancing MRI lesions and clinical relapses.

Our findings indicate that dysregulated expression of Bcl-2 family proteins in peripheral lymphocytes is a feature of clinically active multiple sclerosis.