Open Access Open Access  Restricted Access Subscription Access

Hyaluronan Synthesis, Catabolism, and Signaling in Neurodegenerative Diseases


Affiliations
1 Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, United States
2 Department of Integrative Biosciences, School of Dentistry, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States
3 Department of Pediatrics, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States
 

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 highmolecular weightHA 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.
User
Notifications
Font Size

Abstract Views: 59

PDF Views: 0




  • Hyaluronan Synthesis, Catabolism, and Signaling in Neurodegenerative Diseases

Abstract Views: 59  |  PDF Views: 0

Authors

Larry S. Sherman
Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, United States
Steven Matsumoto
Department of Integrative Biosciences, School of Dentistry, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States
Weiping Su
Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, United States
Taasin Srivastava
Department of Pediatrics, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States
Stephen A. Back
Department of Pediatrics, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States

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 highmolecular weightHA 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.