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Review
. 2023 Nov 30;20(1):286.
doi: 10.1186/s12974-023-02965-w.

Progranulin and GPNMB: interactions in endo-lysosome function and inflammation in neurodegenerative disease

Drew A Gillett  1   2   3 , Rebecca L Wallings  1   2   3 , Oihane Uriarte Huarte #  1   2   3 , Malú Gámez Tansey #  4   5   6   7
Affiliations
Review

Progranulin and GPNMB: interactions in endo-lysosome function and inflammation in neurodegenerative disease

Drew A Gillett et al. J Neuroinflammation. .

Abstract

Background: Alterations in progranulin (PGRN) expression are associated with multiple neurodegenerative diseases (NDs), including frontotemporal dementia (FTD), Alzheimer's disease (AD), Parkinson's disease (PD), and lysosomal storage disorders (LSDs). Recently, the loss of PGRN was shown to result in endo-lysosomal system dysfunction and an age-dependent increase in the expression of another protein associated with NDs, glycoprotein non-metastatic B (GPNMB).

Main body: It is unclear what role GPNMB plays in the context of PGRN insufficiency and how they interact and contribute to the development or progression of NDs. This review focuses on the interplay between these two critical proteins within the context of endo-lysosomal health, immune function, and inflammation in their contribution to NDs.

Short conclusion: PGRN and GPNMB are interrelated proteins that regulate disease-relevant processes and may have value as therapeutic targets to delay disease progression or extend therapeutic windows.

Keywords: Endo-lysosomal system; GPNMB; Immune system; Neurodegenerative diseases; Progranulin.

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Conflict of interest statement

Not applicable.

Figures

Fig. 1
Fig. 1
Diagram of the cell biology of progranulin and GPNMB. Figure created with BioRender.com
Fig. 2
Fig. 2
Summary of progranulin and GPNMB in neurodegenerative disease. Figure created with BioRender.com
See this image and copyright information in PMC

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