Microglial Progranulin: Involvement in Alzheimer’s Disease and Neurodegenerative Diseases
Neurodegenerative diseases such as Alzheimer’s disease have proven resistant to new treatments. The complexity of neurodegenerative disease mechanisms can be highlighted by accumulating evidence for a role for a growth factor, progranulin (PGRN). PGRN is a glycoprotein encoded by the GRN/G...
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| Format: | Article |
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MDPI AG
2019-03-01
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| Series: | Cells |
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| Online Access: | http://www.mdpi.com/2073-4409/8/3/230 |
| _version_ | 1797701865227419648 |
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| author | Anarmaa Mendsaikhan Ikuo Tooyama Douglas G. Walker |
| author_facet | Anarmaa Mendsaikhan Ikuo Tooyama Douglas G. Walker |
| author_sort | Anarmaa Mendsaikhan |
| collection | DOAJ |
| description | Neurodegenerative diseases such as Alzheimer’s disease have proven resistant to new treatments. The complexity of neurodegenerative disease mechanisms can be highlighted by accumulating evidence for a role for a growth factor, progranulin (PGRN). PGRN is a glycoprotein encoded by the GRN/Grn gene with multiple cellular functions, including neurotrophic, anti-inflammatory and lysosome regulatory properties. Mutations in the GRN gene can lead to frontotemporal lobar degeneration (FTLD), a cause of dementia, and neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. Both diseases are associated with loss of PGRN function resulting, amongst other features, in enhanced microglial neuroinflammation and lysosomal dysfunction. PGRN has also been implicated in Alzheimer’s disease (AD). Unlike FTLD, increased expression of PGRN occurs in brains of human AD cases and AD model mice, particularly in activated microglia. How microglial PGRN might be involved in AD and other neurodegenerative diseases will be discussed. A unifying feature of PGRN in diseases might be its modulation of lysosomal function in neurons and microglia. Many experimental models have focused on consequences of PGRN gene deletion: however, possible outcomes of increasing PGRN on microglial inflammation and neurodegeneration will be discussed. We will also suggest directions for future studies on PGRN and microglia in relation to neurodegenerative diseases. |
| first_indexed | 2024-03-12T04:41:50Z |
| format | Article |
| id | doaj.art-4e974167b5f0421fbcffb67fd53c9ad6 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T04:41:50Z |
| publishDate | 2019-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-4e974167b5f0421fbcffb67fd53c9ad62023-09-03T09:35:24ZengMDPI AGCells2073-44092019-03-018323010.3390/cells8030230cells8030230Microglial Progranulin: Involvement in Alzheimer’s Disease and Neurodegenerative DiseasesAnarmaa Mendsaikhan0Ikuo Tooyama1Douglas G. Walker2Molecular Neuroscience Research Center, Shiga University of Medical Science, Otsu 520-2192, JapanMolecular Neuroscience Research Center, Shiga University of Medical Science, Otsu 520-2192, JapanMolecular Neuroscience Research Center, Shiga University of Medical Science, Otsu 520-2192, JapanNeurodegenerative diseases such as Alzheimer’s disease have proven resistant to new treatments. The complexity of neurodegenerative disease mechanisms can be highlighted by accumulating evidence for a role for a growth factor, progranulin (PGRN). PGRN is a glycoprotein encoded by the GRN/Grn gene with multiple cellular functions, including neurotrophic, anti-inflammatory and lysosome regulatory properties. Mutations in the GRN gene can lead to frontotemporal lobar degeneration (FTLD), a cause of dementia, and neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. Both diseases are associated with loss of PGRN function resulting, amongst other features, in enhanced microglial neuroinflammation and lysosomal dysfunction. PGRN has also been implicated in Alzheimer’s disease (AD). Unlike FTLD, increased expression of PGRN occurs in brains of human AD cases and AD model mice, particularly in activated microglia. How microglial PGRN might be involved in AD and other neurodegenerative diseases will be discussed. A unifying feature of PGRN in diseases might be its modulation of lysosomal function in neurons and microglia. Many experimental models have focused on consequences of PGRN gene deletion: however, possible outcomes of increasing PGRN on microglial inflammation and neurodegeneration will be discussed. We will also suggest directions for future studies on PGRN and microglia in relation to neurodegenerative diseases.http://www.mdpi.com/2073-4409/8/3/230neuroinflammationgrowth factoranti-inflammatorymutationamyloidneurodegeneration |
| spellingShingle | Anarmaa Mendsaikhan Ikuo Tooyama Douglas G. Walker Microglial Progranulin: Involvement in Alzheimer’s Disease and Neurodegenerative Diseases Cells neuroinflammation growth factor anti-inflammatory mutation amyloid neurodegeneration |
| title | Microglial Progranulin: Involvement in Alzheimer’s Disease and Neurodegenerative Diseases |
| title_full | Microglial Progranulin: Involvement in Alzheimer’s Disease and Neurodegenerative Diseases |
| title_fullStr | Microglial Progranulin: Involvement in Alzheimer’s Disease and Neurodegenerative Diseases |
| title_full_unstemmed | Microglial Progranulin: Involvement in Alzheimer’s Disease and Neurodegenerative Diseases |
| title_short | Microglial Progranulin: Involvement in Alzheimer’s Disease and Neurodegenerative Diseases |
| title_sort | microglial progranulin involvement in alzheimer s disease and neurodegenerative diseases |
| topic | neuroinflammation growth factor anti-inflammatory mutation amyloid neurodegeneration |
| url | http://www.mdpi.com/2073-4409/8/3/230 |
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