Glycans in Sera of Amyotrophic Lateral Sclerosis Patients and Their Role in Killing Neuronal Cells

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by degeneration of upper and lower motor neurons. To date, glycosylation patterns of glycoproteins in fluids of ALS patients have not been described. Moreover, the aberrant glycosylation related to the pathogenesis of other neurodegenerative diseases encouraged us to explore the glycome of ALS patient sera. We found high levels of sialylated glycans and low levels of core fucosylated glycans in serum-derived N-glycans of patients with ALS, compared to healthy volunteer sera. Based on these results, we analyzed the IgG Fc N297-glycans, as IgG are major serum glycoproteins affected by sialylation or core fucosylation and are found in the motor cortex of ALS patients. The analyses revealed a distinct glycan, A2BG2, in IgG derived from ALS patient sera (ALS-IgG). This glycan increases the affinity of IgG to CD16 on effector cells, consequently enhancing Antibody-Dependent Cellular Cytotoxicity (ADCC). Therefore, we explore whether the Fc-N297-glycans of IgG may be involved in ALS disease. Immunostaining of brain and spinal cord tissues revealed over-expression of CD16 and co-localization of intact ALS-IgG with CD16 and in brain with activated microglia of G93A-SOD1 mice. Intact ALS-IgG enhanced effector cell activation and ADCC reaction in comparison to sugar-depleted or control IgG. ALS-IgG were localized in the synapse between brain microglia and neurons of G93A-SOD1 mice, manifesting a promising in vivo ADCC reaction. Therefore, glycans of ALS-IgG may serve as a biomarker for the disease and may be involved in neuronal damage

Serum anti-Fas antibody levels in amyotrophic lateral sclerosis

In this study, the levels of anti-Fas antibodies were evaluated in patients with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. Sera from 25% of patients with sporadic ALS (sALS) and 22% of patients with familial ALS (fALS) contained abnormal levels of anti-Fas antibodies compared with normal controls. Half of patients with Parkinson's disease (PD), but no patients with Alzheimer's disease (AD), had abnormal levels of anti-Fas antibodies. There was no correlation between the antibody levels of patients with ALS and the length or stage of their disease. These data demonstrate that the peripheral immune system is activated as reflected by anti-Fas antibodies in ALS, but this activation is not specific to ALS. (C) 2003 Elsevier B.V. All rights reserved

Multiple sclerosis and parkinsonism: a case report

Multiple sclerosis (MS) is a well-known disease characterized by the distribution of plaques in the periventricular and subcortical white matter. Although plaques can also be found in the striatum, pallidum and thalamus, extrapyramidal symptoms are very rare in MS. However, the association of MS and parkinsonism is still a controversial topic as it has not been established whether these two conditions occur coincidentally or causally. In the literature, eleven cases of parkinsonism associated with MS have been described. Here, we report a patient with clinically definite MS and signs of parkinsonism. Our patient had slow progressive bradykinesia, static tremor and bradymimia that were not associated with exacerbation or progression of the MS. This rare and interesting association of multiple sclerosis with parkinsonism is discussed in the light of literature reports

PARP expression is increased in astrocytes but decreased in motor neurons in the spinal cord of sporadic ALS patients

The evidence for increased oxidative stress and DNA damage in amyotrophic lateral sclerosis (ALS) prompted studies to determine if the expression of poly(ADP-ribose) polymerase (PARP) is increased in ALS. Using Western analyses of postmortem tissue, we demonstrated that PARP-immunoreactivity (PARP-IR) was increased 3-fold in spinal cord tissues of sporadic ALS (sALS) patients compared with non-neurological disease controls. Despite the increased PARP-IR, PARP mRNA expression was not increased significantly. Immunohistochemical analyses revealed PARP-IR was increased in both white and gray matter of sALS spinal cord. While PARP-IR was predominantly seen in astrocytes, large motor neurons displayed reduced staining compared with controls. This result contrasts sharply to the staining of Alzheimer and MPTP-induced Parkinson diseased tissue, where poly(ADP-ribose) (PAR)-IR was seen mostly in neurons, with little astrocytic staining. PARP-IR was increased in the pellet fraction of sALS homogenates compared with control homogenates, representing potential PARP binding to chromatin or membranes and suggesting a possible mechanism of PARP stabilization. The present results demonstrate glial alterations in sALS spinal cord tissue and support the role of glial alterations in sALS pathogenesis. Additionally, these results demonstrate differences in sALS spinal motor neurons and astrocytes compared to brain neurons and astrocytes in Alzheimer disease and MPTP-induced Parkinson disease despite the presence of markers for oxidative stress in all 3 diseases

A database for screening and registering late onset Pompe disease in Turkey

PMID = 2939567

Importance of Yeasts and Lactic Acid Bacteria in Food Processing

WOS: 000357717400015