The enigmatic roles of microglial versus neuronal progranulin in neurological disease

Excerpt

Progranulin is an ancient, highly conserved gene that regulates cell division, survival, and migration across a wide variety of species. Until the publication of two papers showing that mutations in a single copy of the human GRN gene was the cause of frontotemporal lobar dementia with ubiquitinated TDP-43 inclusions (FTLD-TDP) [2, 5] in 2006, very little was known about the importance of progranulin within the central nervous system. These reports created a strong impetus to identify new mutations and to explore the contribution of this protein in brain health and disease. Within 3 years of the first publications, the Alzheimer Disease and Frontotemporal Dementia Mutation Database (http://​www.​molgen.​ua.​ac.​be/​FTDMutations/​) has grown to encompass 68 distinct GRN mutations in 218 families. …