chondroitin-sulfates and Neurodegenerative-Diseases

The antiinflammatory and antiapoptotic effects of chondroitin sulfate (CS) are being used to treat osteoarthritis. Recent evidence has revealed that those peripheral effects of CS may also have therapeutic interest in diseases of the central nervous system (CNS). We review here such evidence. Perineuronal nets (PNNs) formed by chondroitin sulfate proteoglycans (CSPGs) may have a neuroprotective action against oxidative stress potentially involved in neurodegeneration. On the other hand, in human neuroblastoma SH-SY5Y cells CS has antioxidant and neuroprotective effects by activating the signaling pathway PKC/PI3K/Akt and inducing the antioxidant enzyme hemoxygenase-1. Consistent with this is the observation that protein kinase C (PKC) blockade overcomes inhibition of neurite outgrowth elicited by CSPGs. In addition, CS protects cortical neurons against excytotoxic death by phosphorylation of intracellular signals and the suppression of caspase-3 activation. Of interest is the finding that a disaccharide derived from CSPG degradation (CSGP-DS) protects neurons against toxicity both in vitro and in vivo. Furthermore, CSGP-DS efficiently protects against neuronal loss in experimental autoimmune encephalomyelitis and uveitis, decreases secretion of tumor necrosis factor-alpha (TNF-alpha) and block necrosis factor kappa B (NF-kappaB) translocation. In conclusion, CS may have neuroprotective properties linked to its antioxidant and antiinflammatory effects.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Chondroitin Sulfate Proteoglycans; Chondroitin Sulfates; Humans; Neurodegenerative Diseases; Neuronal Plasticity; Neuroprotective Agents

Glycosaminoglycans (GAGs) are complex polysaccharides, which play important roles in cell growth, differentiation, morphogenesis, cell migration, and bacterial/viral infections. Major GAGs include heparin (Hep)/heparan sulfate, and chondroitin sulfate (CS)/dermatan sulfate (DS). Hep has been used for the treatment of thromboembolic disorders for more than 75 years, and has an established position in therapy today. CS/DS has attracted less attention and its clinical use is limited. However, CS/DS also have intriguing biological activities, which in turn should help in the development of CS/DS-based therapeutics. In this review, the following potential applications of CS/DS chains are discussed. (1) Sugar drugs for parasitic and viral infections. Particular CS variants appear to be involved in infections of various microbes, suggesting that CS/DS oligosaccharide sequences specifically interacting with microbes will lead to the development of inhibitory drugs for these infections. (2) Regenerative medicine. Biological activities of CS/DS chains possibly involve various growth factors, also known as Hep-binding growth factors. Specific CS/DS chains recruit growth/neurotrophic factors and/or potentiate their activities, suggesting that minute amounts of functional CS/DS chains can be utilized for tissue regeneration instead of signaling proteins. (3) Anti-tumor drugs. Specific saccharide structures in CS/DS chains appear to be involved in tumor cell proliferation and metastasis. The detection and identification of such CS/DS saccharide sequences would be an important contribution to cancer therapy.

Topics: Animals; Anti-Infective Agents; Antineoplastic Agents; Chondroitin Sulfates; Dermatan Sulfate; Drug Discovery; Glycosaminoglycans; Humans; Infections; Liver Regeneration; Neoplasms; Neurodegenerative Diseases; Osteoarthritis

Glycan alterations are associated with aging, neuropsychiatric, and neurodegenerative diseases, although the contributions of specific glycan structures to emotion and cognitive functions remain largely unknown. Here, we used a combination of chemistry and neurobiology to show that 4-

Topics: Animals; Chondroitin Sulfates; Extracellular Matrix; Hippocampus; Mice; Neurodegenerative Diseases; Neurons

One major aspect of the aging process is the onset of chronic, low-grade inflammation that is highly associated with age-related diseases. The molecular mechanisms that regulate these processes have not been fully elucidated. We have identified a spontaneous mutant mouse line, small with kinky tail (

Topics: Age Factors; Animals; Apoptosis; Chondroitin Sulfates; Female; Glucuronosyltransferase; Inflammation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Multifunctional Enzymes; Mutation; N-Acetylgalactosaminyltransferases; Neurodegenerative Diseases; Neurons; Protein Processing, Post-Translational; Proteins; Retinal Degeneration

Chondroitin sulfate (CS), a polysaccharide moiety of proteoglycans, is one of the major components of the extracellular matrix in the central nervous system and is involved in various cellular events in the formation and maintenance of the neural network. In the developing brain, CS in the milieu of neural stem/progenitor cells (NSPCs) is believed to participate in the regulation of their functions such as proliferation and differentiation. NSPCs are expected to act as a potent cell type in cell replacement therapy for neurodegeneration in various neurological diseases. Recently, it has been shown that transplantation of NSPCs combined with removal of extracellular CS from the host nervous tissues gives a satisfactory outcome in some animal models of nervous tissue injuries including neonatal hypoxic-ischemic injury and adult spinal cord injury. The combination of cell transplantation with modification of the extracellular matrix of the host tissue could be a novel strategy for the treatment of incurable neurodegenerative diseases.

Topics: Animals; Cell- and Tissue-Based Therapy; Central Nervous System; Chondroitin Sulfates; Humans; Nerve Degeneration; Neurodegenerative Diseases; Neurons; Stem Cell Transplantation; Stem Cells