Recent Insights into the Involvement of Progranulin in Frontotemporal Dementia

Li      Sun; Jason      L. Eriksen

doi:10.2174/157015911798376361

Abstract

Progranulin is a widely expressed protein that is involved in the regulation of multiple biological processes, including embryogenesis, host defense, and wound repair. In the central nervous system, progranulin is constitutively expressed at modest levels in neurons and microglia, but shows dramatic microglial immunoreactivity in degenerative diseases that exhibit prominent neuroinflammation. In addition to the role that PGRN plays in the periphery, its expression is of critical importance in brain health, as demonstrated by recent discovery that progranulin haploinsufficiency results in familial frontotemporal lobar degeneration. Since progranulin deficiency was first described, there has been an intense ongoing effort to decipher the mysterious role that this protein plays in dementia. This review provides an update on our understanding of the possible neuronal function and discusses the challenging problems related to progranulin expression within genetics, cell biology, and neurodegeneration.

Keywords: progranulin, Frontotemporal lobar degeneration, TDP-43, Alzheimer's disease, epithelial cells, amino acids, 6kDa peptides, granulin fragment GRN-E