Progranulins

Cysteine-rich, precursor glycoproteins encoded by the granulin gene (GRN). They contain granulin-repeats separated by linker sequences that are cleaved by a variety of proteases to release the individual GRANULIN PEPTIDES. The mammalian progranulin is composed of a half-granulin repeat followed by 7 granulin repeats. The mammalian GRANULINS are named PARAGRANULIN and granulin 1-7 for their order in the progranulin propeptide. Progranulin has growth-factor like effects and is expressed over a broad range of tissues. Under-expression of progranulin is linked to neurodegenerative diseases including FRONTOTEMPORAL DEMENTIA and NEURONAL CEROID LIPOFUSCINOSIS, while over-expression is linked to metabolic diseases including OBESITY, and INSULIN RESISTANCE.

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Networked: 1142 relevant articles (23 outcomes, 123 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Experts

1.	Rademakers, Rosa: 64 articles (01/2021 - 08/2006)
2.	Galimberti, Daniela: 41 articles (08/2022 - 07/2008)
3.	Serrero, Ginette: 36 articles (05/2022 - 01/2003)
4.	Scarpini, Elio: 35 articles (01/2018 - 07/2008)
5.	Dickson, Dennis W: 33 articles (01/2021 - 11/2006)
6.	Miller, Bruce L: 32 articles (01/2021 - 03/2007)
7.	Rohrer, Jonathan D: 26 articles (12/2022 - 03/2008)
8.	Van Broeckhoven, Christine: 24 articles (01/2022 - 08/2006)
9.	Fenoglio, Chiara: 24 articles (01/2018 - 01/2009)
10.	Ghidoni, Roberta: 21 articles (01/2020 - 03/2008)

Related Diseases

1.	Frontotemporal Lobar Degeneration (Degeneration, Frontotemporal Lobar) 01/01/2020 - "Our next secreted chaperone is progranulin; polymorphisms in this gene represent a known genetic risk factor for frontotemporal lobar degeneration, and progranulin overexpression has been found to be effective in reducing Alzheimer's- and Parkinson's-like neurodegenerative phenotypes in mouse models. " 11/01/2011 - "This review highlights the importance of genetic studies in the context of FTLD and further emphasizes the need for future genetic and cell biology research to continue the effort in finding a cure for progranulin-related diseases." 01/01/2018 - "TMEM106B-related and GFRA2-related pathways might be future targets for treatments for FTLD, but the biological interaction between progranulin and these potential disease modifiers requires further study. " 02/01/2016 - "Missense mutations in progranulin gene associated with frontotemporal lobar degeneration: study of pathogenetic features." 01/01/2011 - "A morphometric study of the spatial patterns of TDP-43 immunoreactive neuronal inclusions in frontotemporal lobar degeneration (FTLD) with progranulin (GRN) mutation."
2.	Frontotemporal Dementia (Semantic Dementia) 07/19/2017 - "Loss of TMEM106B Ameliorates Lysosomal and Frontotemporal Dementia-Related Phenotypes in Progranulin-Deficient Mice." 01/01/2019 - "White matter hyperintensities in progranulin-associated frontotemporal dementia: A longitudinal GENFI study." 05/01/2009 - "On the other hand, several previous studies have demonstrated that the most frequent first syndrome of FTLD-TDP with progranulin gene (PGRN) mutations is FTD and that neuronal loss in the frontal cortex is more severe than that in the temporal cortex. " 10/01/2008 - "Recent studies demonstrated that progranulin plays an integral role in the pathogenesis of frontotemporal dementia. " 11/27/2023 - "Analytical and clinical validation of a blood progranulin ELISA in frontotemporal dementias."
3.	Inflammation (Inflammations) 11/01/2023 - "The acute increase in ISF progranulin after LPS treatment is consistent with a role for extracellular progranulin in regulating inflammation, and may have been driven by microglia or peripheral immune cells. " 02/01/2023 - "High serum progranulin levels were observed in frail older adults and were associated with worse physical function and increased chronic inflammation. " 05/10/2022 - "pylori, affecting the response of progranulin against gastric inflammation." 01/01/2020 - "Microglia produce high levels of progranulin, and reduction of progranulin in microglia alone is sufficient to recapitulate inflammation, lysosomal dysfunction, and hyperproliferation in a cell-autonomous manner. " 01/01/2020 - "Progranulin (PGRN) has potential anti-inflammation action, however, the effect of PGRN on macrophage M1 polarization has been poorly studied. "
4.	Brain Ischemia (Cerebral Ischemia) 01/01/2018 - "The aim of this study is to explore the effect progranulin (PGRN) has on endoplasmic reticulum (ER) stress and the NF-κB activation in reactive astrocytes found in rat models with focal cerebral ischemia-reperfusion (I/R) injury. " 01/01/2023 - "Progranulin released from microglial lysosomes reduces neuronal ferroptosis after cerebral ischemia in mice." 01/01/2022 - "Progranulin significantly alleviated anxiety-like behavior and spatial learning and memory impairment induced by cerebral ischemia in mice. " 01/01/2021 - "Progranulin promotes functional recovery and neurogenesis in the subventricular zone of adult mice after cerebral ischemia." 05/07/2020 - "Corrigendum to "Progranulin protects against cerebral ischemia-reperfusion (I/R) injury by inhibiting necroptosis and oxidative stress" [Biochem. "
5.	Reperfusion Injury 05/01/2015 - "Progranulin protects against renal ischemia/reperfusion injury in mice." 11/01/2021 - "Retraction: "Protective effects of Progranulin against focal cerebral ischemia-reperfusion injury in rats by suppressing endoplasmic reticulum stress and NF-κB activation in reactive astrocytes," by Qing Shu, Hua Fan, Shi-Jun Li, Dan Zhou, Wei Ma, Xiao-Yan Zhao, Jun-Qiang Yan, Gang Wu, J Cell Biochem. " 01/01/2018 - "Protective effects of Progranulin against focal cerebral ischemia-reperfusion injury in rats by suppressing endoplasmic reticulum stress and NF-κB activation in reactive astrocytes." 01/01/2020 - "In this study, we investigated the effects of progranulin on myocardial ischemia and reperfusion injury. " 10/01/2023 - "We have previously shown that the administration of recombinant progranulin (PGRN) protects against myocardial ischemia and reperfusion injury. "

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