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Hyaluronan Synthesis, Catabolism, and Signaling in Neurodegenerative Diseases.

Sherman LS, Matsumoto S, Su W, Srivastava T, Back SA - Int J Cell Biol (2015)

Bottom Line: HA is found throughout the CNS as a constituent of proteoglycans, especially within perineuronal nets that have been implicated in regulating neuronal activity.HA is also found in the white matter where it is diffusely distributed around astrocytes and oligodendrocytes.Hyaluronidases that digest high molecular weight HA into smaller fragments are also elevated following CNS insults and can generate HA digestion products that have unique biological activities.

View Article: PubMed Central - PubMed

Affiliation: Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA ; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.

ABSTRACT
The glycosaminoglycan hyaluronan (HA), a component of the extracellular matrix, has been implicated in regulating neural differentiation, survival, proliferation, migration, and cell signaling in the mammalian central nervous system (CNS). HA is found throughout the CNS as a constituent of proteoglycans, especially within perineuronal nets that have been implicated in regulating neuronal activity. HA is also found in the white matter where it is diffusely distributed around astrocytes and oligodendrocytes. Insults to the CNS lead to long-term elevation of HA within damaged tissues, which is linked at least in part to increased transcription of HA synthases. HA accumulation is often accompanied by elevated expression of at least some transmembrane HA receptors including CD44. Hyaluronidases that digest high molecular weight HA into smaller fragments are also elevated following CNS insults and can generate HA digestion products that have unique biological activities. A number of studies, for example, suggest that both the removal of high molecular weight HA and the accumulation of hyaluronidase-generated HA digestion products can impact CNS injuries through mechanisms that include the regulation of progenitor cell differentiation and proliferation. These studies, reviewed here, suggest that targeting HA synthesis, catabolism, and signaling are all potential strategies to promote CNS repair.

No MeSH data available.


Related in: MedlinePlus

Distribution of HA (white) in lumbar spinal cord white matter (WM) and gray matter (GM). A section of a rat spinal cord was labeled with a biotinylated-HA-binding protein then visualized by fluorescence microscopy following staining with fluorescein-labeled streptavidin. Note that HA is diffusely distributed throughout white matter, but is much more dense in gray matter.
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fig1: Distribution of HA (white) in lumbar spinal cord white matter (WM) and gray matter (GM). A section of a rat spinal cord was labeled with a biotinylated-HA-binding protein then visualized by fluorescence microscopy following staining with fluorescein-labeled streptavidin. Note that HA is diffusely distributed throughout white matter, but is much more dense in gray matter.

Mentions: In the uninjured CNS, HA is diffusely distributed throughout the white matter but is densely packed in gray matter, including perineuronal nets (Figure 1). Damage to the CNS leads to HA accumulation [4, 18] in both white and gray matter that can persist for long periods of time after the initial insult. In most cases, pathological elevation of HA is linked to increased HAS transcription and is often associated with reactive astrogliosis and glial scarring. This effect has been most thoroughly studied in the context of ischemic injuries. For example, HAS2 mRNA is normally expressed at very low levels in the CNS but increased significantly within 6 hours following middle cerebral artery occlusion in rats [19]. HA was also elevated up to six weeks following a photothrombotic stroke lesion in adult mouse cortex [20]. Consistent with these experimental findings, HAS1 and HAS2 are elevated in infarcted and peri-infarcted tissues from patients following ischemic stroke [21]. Plasma levels of HA were also significantly elevated in acute stroke patients compared to controls and could predict 3-month functional outcomes, especially in patients with intracerebral hemorrhage [22].


Hyaluronan Synthesis, Catabolism, and Signaling in Neurodegenerative Diseases.

Sherman LS, Matsumoto S, Su W, Srivastava T, Back SA - Int J Cell Biol (2015)

Distribution of HA (white) in lumbar spinal cord white matter (WM) and gray matter (GM). A section of a rat spinal cord was labeled with a biotinylated-HA-binding protein then visualized by fluorescence microscopy following staining with fluorescein-labeled streptavidin. Note that HA is diffusely distributed throughout white matter, but is much more dense in gray matter.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4581574&req=5

fig1: Distribution of HA (white) in lumbar spinal cord white matter (WM) and gray matter (GM). A section of a rat spinal cord was labeled with a biotinylated-HA-binding protein then visualized by fluorescence microscopy following staining with fluorescein-labeled streptavidin. Note that HA is diffusely distributed throughout white matter, but is much more dense in gray matter.
Mentions: In the uninjured CNS, HA is diffusely distributed throughout the white matter but is densely packed in gray matter, including perineuronal nets (Figure 1). Damage to the CNS leads to HA accumulation [4, 18] in both white and gray matter that can persist for long periods of time after the initial insult. In most cases, pathological elevation of HA is linked to increased HAS transcription and is often associated with reactive astrogliosis and glial scarring. This effect has been most thoroughly studied in the context of ischemic injuries. For example, HAS2 mRNA is normally expressed at very low levels in the CNS but increased significantly within 6 hours following middle cerebral artery occlusion in rats [19]. HA was also elevated up to six weeks following a photothrombotic stroke lesion in adult mouse cortex [20]. Consistent with these experimental findings, HAS1 and HAS2 are elevated in infarcted and peri-infarcted tissues from patients following ischemic stroke [21]. Plasma levels of HA were also significantly elevated in acute stroke patients compared to controls and could predict 3-month functional outcomes, especially in patients with intracerebral hemorrhage [22].

Bottom Line: HA is found throughout the CNS as a constituent of proteoglycans, especially within perineuronal nets that have been implicated in regulating neuronal activity.HA is also found in the white matter where it is diffusely distributed around astrocytes and oligodendrocytes.Hyaluronidases that digest high molecular weight HA into smaller fragments are also elevated following CNS insults and can generate HA digestion products that have unique biological activities.

View Article: PubMed Central - PubMed

Affiliation: Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA ; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.

ABSTRACT
The glycosaminoglycan hyaluronan (HA), a component of the extracellular matrix, has been implicated in regulating neural differentiation, survival, proliferation, migration, and cell signaling in the mammalian central nervous system (CNS). HA is found throughout the CNS as a constituent of proteoglycans, especially within perineuronal nets that have been implicated in regulating neuronal activity. HA is also found in the white matter where it is diffusely distributed around astrocytes and oligodendrocytes. Insults to the CNS lead to long-term elevation of HA within damaged tissues, which is linked at least in part to increased transcription of HA synthases. HA accumulation is often accompanied by elevated expression of at least some transmembrane HA receptors including CD44. Hyaluronidases that digest high molecular weight HA into smaller fragments are also elevated following CNS insults and can generate HA digestion products that have unique biological activities. A number of studies, for example, suggest that both the removal of high molecular weight HA and the accumulation of hyaluronidase-generated HA digestion products can impact CNS injuries through mechanisms that include the regulation of progenitor cell differentiation and proliferation. These studies, reviewed here, suggest that targeting HA synthesis, catabolism, and signaling are all potential strategies to promote CNS repair.

No MeSH data available.


Related in: MedlinePlus