Progranulin as a therapeutic target in neurodegenerative diseases.

Progranulin (PGRN, encoded by the GRN gene) plays a key role in the development, survival, function, and maintenance of neurons and microglia in the mammalian brain. It regulates lysosomal biogenesis, inflammation, repair, stress response, and aging. GRN loss-of-function mutations cause neuronal ceroid lipofuscinosis or frontotemporal dementia-GRN (FTD-GRN) in a gene dosage-dependent manner. Mutations that reduce PGRN levels increase the risk for developing Alzheimer's disease, Parkinson's disease, and limbic-predominant age-related transactivation response DNA-binding protein 43 encephalopathy, as well as exacerbate the progression of amyotrophic lateral sclerosis (ALS) and FTD caused by the hexanucleotide repeat expansion in the C9orf72 gene. Elevating and/or restoring PGRN levels is an attractive therapeutic strategy and is being investigated for neurodegenerative diseases through multiple mechanisms of action. Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Citation

Herve Rhinn, Nadine Tatton, Stella McCaughey, Michael Kurnellas, Arnon Rosenthal. Progranulin as a therapeutic target in neurodegenerative diseases. Trends in pharmacological sciences. 2022 Aug;43(8):641-652

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PMID: 35039149

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