Progranulin in neurodegenerative dementia

Long‐term or severe lack of protective factors is important in the pathogenesis of neurodegenerative dementia. Progranulin (PGRN), a neurotrophic factor expressed mainly in neurons and microglia, has various neuroprotective effects such as anti‐inflammatory effects, promoting neuron survival and neurite growth, and participating in normal lysosomal function. Mutations in the PGRN gene (GRN) have been found in several neurodegenerative dementias, including frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). Herein, PGRN deficiency and PGRN hydrolytic products (GRNs) in the pathological changes related to dementia, including aggregation of tau and TAR DNA‐binding protein 43 (TDP‐43), amyloid‐β (Aβ) overproduction, neuroinflammation, lysosomal dysfunction, neuronal death, and synaptic deficit have been summarized. Furthermore, as some therapeutic strategies targeting PGRN have been developed in various models, we highlighted PGRN as a potential anti‐neurodegeneration target in dementia. Long‐term or severe lack of protective factors is important in the pathogenesis of neurodegenerative dementia. Progranulin (PGRN), a neurotrophic factor expressed mainly in neurons and microglia, has various neuroprotective effects such as anti‐inflammatory effects, promoting neuron survival and neurite growth, and participating in normal lysosomal function. Mutations in the PGRN gene (GRN) have been found in several neurodegenerative dementias, including frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). This Review summarizes PGRN deficiency and PGRN hydrolytic products (GRNs) in the pathological changes related to dementia, including aggregation of tau and TAR DNA‐binding protein 43 (TDP‐43), amyloid‐β (Aβ) overproduction, neuroinflammation, lysosomal dysfunction, neuronal death, and synaptic deficit. Furthermore, as some therapeutic strategies targeting PGRN have been developed in various models, we highlighted PGRN as a potential anti‐neurodegeneration target in dementia.