Molecular Basis of Multiple Sclerosis

2005 ◽  
Vol 88 (3) ◽  
pp. 157-202 ◽  
Author(s):  
Anthony K. Campbell ◽  
Jonathan P. Waud ◽  
Stephanie B. Matthews

A staggering 4000 million people cannot digest lactose, the sugar in milk, properly. All mammals, apart from white Northern Europeans and few tribes in Africa and Asia, lose most of their lactase, the enzyme that cleaves lactose into galactose and glucose, after weaning. Lactose intolerance causes gut and a range of systemic symptoms, though the threshold to lactose varies considerably between ethnic groups and individuals within a group. The molecular basis of inherited hypolactasia has yet to be identified, though two polymorphisms in the introns of a helicase upstream from the lactase gene correlate closely with hypolactasia, and thus lactose intolerance. The symptoms of lactose intolerance are caused by gases and toxins produced by anaerobic bacteria in the large intestine. Bacterial toxins may play a key role in several other diseases, such as diabetes, rheumatoid arthritis, multiple sclerosis and some cancers. The problem of lactose intolerance has been exacerbated because of the addition of products containing lactose to various foods and drinks without being on the label. Lactose intolerance fits exactly the illness that Charles Darwin suffered from for over 40 years, and yet was never diagnosed. Darwin missed something else – the key to our own evolution – the Rubicon some 300 million years ago that produced lactose and lactase in sufficient amounts to be susceptible to natural selection.


2005 ◽  
Vol 7 (3) ◽  
pp. 1-17 ◽  
Author(s):  
Samantha Holmes ◽  
Manuel A. Friese ◽  
Christian Siebold ◽  
E. Yvonne Jones ◽  
John Bell ◽  
...  

Multiple sclerosis (MS) is an autoimmune disease with an important genetic component. The strongest genetic association is with the major histocompatibility complex (MHC) region. Several MHC alleles predispose to the disease, the most prominent of which are certain alleles in the HLA-DR2 haplotype. Functional and structural studies have helped to explain the molecular basis of these associations. Although there is currently no curative treatment for MS, an increased understanding of the disease has aided the design of immunotherapies that act on the immune system more specifically than the longstanding drugs. Many of these therapies work at the antigen-specific level, disrupting the interaction between T-cell receptors and MHC molecules that leads to disease.


2011 ◽  
Vol 18 (5) ◽  
pp. 569-577 ◽  
Author(s):  
Haritz Irizar ◽  
Maider Muñoz-Culla ◽  
Olaia Zuriarrain ◽  
Estibaliz Goyenechea ◽  
Tamara Castillo-Triviño ◽  
...  

Background: The association between multiple sclerosis (MS) and the HLA-DRB1*15:01 haplotype has been proven to be strong, but its molecular basis remains unclear. Vitamin D receptor (VDR) gene variants and sex have been proposed to modulate this association. Objectives: 1) Test the association of MS with *15:01 and VDR variants; 2) check whether VDR variants and/or sex modulate the risk conferred by *15:01; 3) study whether *15:01, VDR variants and/or sex affect HLA II gene expression. Methods: Peripheral blood from 364 MS patients and 513 healthy controls was obtained and DNA and total RNA were extracted from leukocytes. HLA-DRB1, DRB5 and DQA1 gene expression measurements and *15:01 genotyping were performed by qPCR. VDR variants were genotyped by PCR-RFLP. Results: Our data confirms that the *15:01 haplotype confers a higher risk of suffering from MS (OR = 1.364; 95% CI = 1.107–1.681). No association was found between VDR variants and MS, but they were shown to moderately modulate the risk conferred by *15:01. Sex confers a much stronger modulation and the *15:01-MS association seems to be female specific. A higher *15:01 frequency has been observed in Basques (45.1%). *15:01 positive samples showed a significant overexpression of DRB1 ( p < 0.001), DRB5 ( p < 0.001) and DQA1 ( p = 0.004) in patients. DRB1 ( p = 0.004) and DRB5 ( p < 0.001) were also overexpressed in *15:01 controls. Conclusions: We confirm the *15:01-MS association and support that it is female specific. The relevance of ethnic origin on association studies has also been highlighted. HLA-DRB1*15:01 seems to be a haplotype consistently linked to high HLA II gene expression.


FEBS Letters ◽  
2011 ◽  
Vol 585 (23) ◽  
pp. 3715-3723 ◽  
Author(s):  
Hans Lassmann ◽  
Jack van Horssen

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Paolo Riccio ◽  
Rocco Rossano ◽  
Grazia Maria Liuzzi

Multiple sclerosis is a complex and multifactorial neurological disease, and nutrition is one of the environmental factors possibly involved in its pathogenesis. At present, the role of nutrition is unclear, and MS therapy is not associated to a particular diet. MS clinical trials based on specific diets or dietary supplements are very few and in some cases controversial. To understand how diet can influence the course of MS and improve the wellness of MS patients, it is necessary to identify the dietary molecules, their targets and the molecular mechanisms involved in the control of the disease. The aim of this paper is to provide a molecular basis for the nutritional intervention in MS by evaluating at molecular level the effect of dietary molecules on the inflammatory and autoimmune processes involved in the disease.


2012 ◽  
Vol 9 (1) ◽  
Author(s):  
Alexander Hundeshagen ◽  
Michael Hecker ◽  
Brigitte Katrin Paap ◽  
Charlotte Angerstein ◽  
Ole Kandulski ◽  
...  

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