Wpongster8

Hi Wponster8,

You've done a great job expanding the article and I'm impressed by how much the article covers. That being said, I think you need to add more links throughout the entire article so that the reader might be able to click on a related term and learn more. Additionally, I think it can be confusing for the reader at times because you talk more about progranulin than granulin so I think you might want to talk more about granulin in your intro and try to bring up more granulin specific information throughout the article. I've listed suggestions for each section of your article below and I highly recommend you reread through your article and correct any grammar erros. Please let me know if you need anything clarified and good luck.

-Naironfire

Introduction:

- you mention that granulin comes from progranulin which has a variety functions but you don't really specify what granulin does. Even if granulin has several functions, I would recommend bringing up one or two example functions. Also, you might want to try and add more relevant information about granulin in your intro instead of having most of the intro about progranulin.

-You may want to delete the last sentence about Progranulin's involvement because most people reading this won't really understand and it can be discussed later on.

Structure:

-Can you maybe be more specific and name the family of proteins that granulin belongs to if the name exists? Also does being a member of that hormone family reveal what granulin does? Does granulin have a similar function?

-Can you clarify/add a link/explain what glycosylated means

Progranulin Expression:

-this section is well written. I would recommend adding links on certain words wherever you can so readers can look up a term they might not fully understand. For example, you can link the central nervous system, peripheral nervous system, astrocytes, glial cells etc.

-If you have time to research, can you maybe add why pogranulin is expressed in the brain?

Progranulin:

-What does it mean for the smaller cleavage products to be synonymous with granulins A and B? I think this could use more clarification. Also what are Epithelins?

- You might want to move up your sentence about Elastase after your first sentence. So that you explain how granulin is cleaved before you start talking about the cleavage products

Intracellular Trafficking:

-Can you add any links here? This may help if the reader doesn't really know some of these terms

Function:

Would recommend adding links where you can

-Can you further clarify how progranulin is involved in lysosomal function?

-Also, if possible can you add a year/scientist attribute to when the GRN mutation was discovered or who did it?

Clinical Significance:

-Add links where possible

Other Diseases:

Impaired protein degradation in FTLD and

related disorders (Gotzl et al., 2016) provides a basic review of different genes hypothesized to be a cause of impaired protein degradation in the pathogenesis of patients with FTLD. There are two sections that related mutations in GRN to both FTD and NCL.

Progranulin, lysosomal regulation and neurodegenerative disease (Kao et al., 2017) reviews hypothesized functions of GRN. There is a heavier emphasis on how extracellular progranulin is endocytosed and trafficked to the lysosome, as well as current evidence as to why progranulin might be involved in protein homeostasis in the cell.

Progranulin: at the interface of neurodegenerative and metabolic diseases (Nguyen et al., 2013) attempts to review the role of progranulin in type 2 diabetes, obesity, atherosclerosis, providing a good overview of how progranulin may influence metabolic function in the cell.

Progranulin in neurodegenerative disease (Petkau et al., 2014) reviews in further depth the role of progranulin neurodegeneration by describing its function in neurons and microglia. There is also a brief update on the different progranulin studies conducted on mice.

Individuals with progranulin haploinsufficiency exhibit features of neuronal ceroid lipofuscinosis (Ward et al., 2017) used retinal imaging studies, and examined post-mortem tissue, lymphoblasts and fibroblasts to investigate whether individuals with the GRN heterozygous mutation have features that are also present in individuals with the GRN double mutant, which causes NCL. They found a build-up of lipofuscin and NCL-like storage material build up, further corroborating progranulin's role in lysosomal function and regulation.

Peer Feedback (Alisa Chuang)

Overall:

• As a general recommendation, use more proper pronouns instead of "it" for clarity.
• In terms of article/paragraph structures, there is a nice flow of information. I would recommend breaking up the text into more paragraphs to make it more readable.
• I like how you used multiple citations for single sentences.
• I think the introduction was generally pretty clear, and that the titles of the subsections accurately described their contents.
• In addition, the order of the sections mostly make sense, as does the lead of each section.
• I didn't feel like the writing was biased, nor did I see any major grammatical issues.
• I would like to see slightly more basic vocabulary used, as it does seem a bit technical for the average reader.
• Though the writing was a bit technical, the parts that I could understand with little background were interesting.

Specifically:

• I think there is a disproportionate amount of space dedicated to clinical significance, however interesting it may be.
• I would also recommend reorganizing the subsections so that the progranulin section comes before the progranulin expression section. I also expected the function subsection to be earlier in the article, but that might be more of a preference thing.
• Some estimate of ages or prevalence in the clinical significance section could be added.
• Slightly more citations in the progranulin section could be added.
• Images of progranulin or any of the sections mentioned in clinical significance, or even possibly something related to wound healing could be added.

Alisachuang (talk) 21:58, 31 May 2018 (UTC)