Matters of size: Roles of hyaluronan in CNS aging and disease

Involvement of extracellular matrix (ECM) components in aging and age-related neurodegeneration is not well understood. The role of hyaluronan (HA), a major extracellular matrix glycosaminoglycan, in malignancy and inflammation is gaining new understanding. In particular, the differential biological effects of high molecular weight (HMW-HA) and low molecular weight hyaluronan (LMW-HA), and the mechanism behind such differences are being uncovered. Tightly regulated in the brain, HA can have diverse effects on cellular development, growth and degeneration. In this review, we summarize the homeostasis and signaling of HA in healthy tissue, discuss its distribution and ontogeny in the central nervous system (CNS), summarize evidence for its involvement in age-related neurodegeneration and Alzheimer Disease (AD), and assess the potential of HA as a therapeutic target in the CNS.