Abstract
GRN mutations cause frontotemporal lobar degeneration with TDP-43-positive inclusions. The mechanism of pathogenesis is haploinsufficiency. Recently, homozygous GRN mutations were detected in two patients with neuronal ceroid lipofuscinosis, a lysosomal storage disease. It is unknown whether the pathogenesis of these two conditions is related. Progranulin is cleaved into smaller peptides called granulins. Progranulin and granulins are attributed with roles in cancer, inflammation, and neuronal physiology. Cell surface receptors for progranulin, but not granulin peptides, have been reported. Revealing the cell surface receptors and the intracellular functions of granulins and progranulin is crucial for understanding their contributions to neurodegeneration.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Frontotemporal Lobar Degeneration / genetics
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Frontotemporal Lobar Degeneration / metabolism*
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Homozygote
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Humans
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Inflammation / genetics
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Inflammation / metabolism
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / metabolism*
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Mutation*
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Neoplasms / genetics
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Neoplasms / metabolism
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Neuronal Ceroid-Lipofuscinoses / genetics
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Neuronal Ceroid-Lipofuscinoses / metabolism*
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Progranulins
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Proteolysis*
Substances
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GRN protein, human
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Intercellular Signaling Peptides and Proteins
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Neoplasm Proteins
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Nerve Tissue Proteins
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Progranulins