Hyaluronan Synthesis, Catabolism, and Signaling in Neurodegenerative Diseases

Figure 3

A single OL (blue cell) can form myelin (yellow) for multiple internodes of the same axon (gray) or for many axons. In uninjured white matter, HA (red) is diffuse while in perineuronal nets HA is at much higher density (not shown). Following injury, myelin and oligodendrocytes are destroyed and HA is initially disrupted. HA later accumulates at higher than normal levels coincident with the appearance of reactive astrocytes (orange cells). CD44 and possibly other HA receptors (purple) are elevated on astrocytes and OPCs recruited to lesions. Both astrocytes and recruited OPCs (green cell) then express hyaluronidases (including PH20; black arrows in lower panel) that digest the excess HA within lesions. The resulting HA digestion products that accumulate in the injury microenvironment feed back on OPCs (blue arrow in lower panel) and prevent their differentiation and subsequent remyelination.