Step 4: Research‎ > ‎

Progranulin

Loss-of-function mutations in the gene encoding for the protein progranulin (PGRN) have been found in patients with hereditary FTD. Progranulin is thought to be a growth factor secreted by cells that is implicated in a wide range of biological functions. FTD patients with progranulin mutations have only one working copy of the progranulin gene and consequently have much lower levels of progranulin. In addition, progranulin-deficient mouse models of FTD have been found to have severe disabilities with FTD-like behavioral and neuropathological deficits. Though progranulin’s function is not fully understood, studies have found it to be involved in the inflammatory response. In addition, progranulin has been found to be up-regulated in damaged tissue, leading to proposals that progranulin is involved in the wound repair process. It has also been found to have increased expression in a wide range of inflammatory immune disorders, such as arthritis.

Recently, the link between progranulin and its vital role in defending against prolonged inflammation was further strengthened when scientists found that progranulin could potentially counteract tumor necrosis factor-alpha (TNF-α), a major pro-inflammatory cytokine that stimulates activation of the inflammatory response (Tang, et al., 2011). Progranulin was found to bind to TNF-α’s receptors, thus probably blocking interaction between TNF-α and its receptors. This could prevent TNF-α from activating the inflammatory response, supporting the idea that progranulin could be essential in preventing chronic inflammation, and insufficient levels of it could lead to diseases like FTD.

We based our idea on this finding, and progranulin was our initial focus.


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