Progranulin is the precursor protein for granulin. Cleavage of progranulin produces a variety of active 6 kDa granulin peptides. These smaller cleavage products are named granulin A, granulin B, granulin C, etc. Cleavage of progranulin into granulin occurs either in the extracellular matrix or the lysosome. Elastase, proteinase 3 and matrix metalloproteinase are proteases capable of cleaving progranulin into individual granulin peptides. While progranulin is associated with anti-inflammation, cleaved granulin peptides have been implicated in pro-inflammatory behavior. Progranulin is hypothesized to be a neurotrophic factor involved in corticogenisis. Progranulin levels are elevated when tissue is inflamed. After wounding, keratinocytes, macrophages and neutrophils increase production of progranulin. Progranulin may also be involved in cancer development, atherosclerosis and other metabolic disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS) and limbic predominant age-related TDP-43 encephalopathy (LATE).
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