Progranulin deficiency in the brain: the interplay between neuronal and non-neuronal cells.

ABSTRACT: Heterozygous mutations in GRN gene lead to insufficient levels of the progranulin (PGRN) protein, resulting in frontotemporal dementia (FTD) with TAR DNA-binding protein 43 (TDP-43) inclusions, classified pathologically as frontotemporal lobar degeneration (FTLD-TDP). Homozygous GRN mutations are exceedingly rare and cause neuronal ceroid lipofuscinosis 11, a lysosomal storage disease with onset in young adulthood, or an FTD syndrome with late-onset manifestations. In this review, we highlight the broad spectrum of clinical phenotypes associated with PGRN deficiency, including primary progressive aphasia and behavioral variant of frontotemporal dementia. We explore these phenotypes alongside relevant rodent and in vitro human models, ranging from the induced pluripotent stem cell-derived n

SUBMITTER: Gaweda-Walerych K 

PROVIDER: S-EPMC12001433 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature