Week 10: Final Product

We’re nearing the end of this project!

As I’ve finished the wet lab portion of my project last week, this week I’ve been working on my final product, a mini paper. Although I’ve spent the whole week working on this paper, a lot of this involved shortening all the blogs I’ve written over the course of this project. Because this wouldn’t be new information, below is a little look into just the introduction I’ve rewritten, now that I’m nearing the completion of my project and have refined its direction.

Introduction

Frontotemporal dementia (FTD) is a neurodegenerative disease caused by frontotemporal lobar degeneration (FTLD) (1). Around half of FTLD patients possess TAR DNA binding protein 43 (TDP-43) inclusions, making up the largest category, FTLD-TDP (2-3).

Transmembrane protein 106B (TMEM106B) is a protein whose genetic variations have been found to be a key driver of FTLD-TDP (4-8). TMEM106B resides within the membranes of late endosomes and lysosomes and plays important roles in regulating transportation and maturation within the lysosome (9).

The TMEM106B protein is made of three domains: the N-terminal suspended in the cell’s cytoplasm, the transmembrane domain, and the C-terminal suspended within the lysosome (10-11). Cryo-electron microscopy points to pathological C-terminal fragments forming amyloid fibrils in patients with FTLD-TDP (12-15). These insoluble fragments contribute to decreased TDP-43 function (1).

Although TMEM106B filaments are a normal part of aging, genetic variations lead to differential expressions of FTLD-TDP (1). Patients who possess the TMEM106B rs3173615 protective allele experience a slowdown of FTLD-TDP progression, along with postmortem samples showing little aggregation, in contrast to increased levels for those with the risk allele (1). Those with the protective allele saw increased levels of TMEM106B dimers, suggesting the role of dimers in limiting fibril formation (1).

[…] (this section is cut out for confidentiality)

To further understand the impact of TMEM106B monomerization on FTLD-TDP disease progression, this study will investigate the differences between the proteomes of TMEM106B monomers and dimers.

References

1. Marks https://pmc.ncbi.nlm.nih.gov/articles/PMC10841341/
2. Arai https://www.sciencedirect.com/science/article/pii/S0006291X06023187?via%3Dihub
3. Neumann https://pubmed.ncbi.nlm.nih.gov/17356379/
4. Gallagher ​​https://pmc.ncbi.nlm.nih.gov/articles/PMC4003885/
5. Blitterswijk https://pmc.ncbi.nlm.nih.gov/articles/PMC3944829/
6. Cruchaga https://pmc.ncbi.nlm.nih.gov/articles/PMC3090529/
7. Finch https://pmc.ncbi.nlm.nih.gov/articles/PMC3034409/
8. Van Deerlin https://pmc.ncbi.nlm.nih.gov/articles/PMC2828525/
9. Jiao https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-023-00644-1
10. Lang https://www.jbc.org/article/S0021-9258(20)49998-3/fulltext
11. Stagi https://pmc.ncbi.nlm.nih.gov/articles/PMC4145808/ 
12. Chang https://pmc.ncbi.nlm.nih.gov/articles/PMC9018563/
13. Fan https://pubmed.ncbi.nlm.nih.gov/35477998/ 
14. Jiang https://pmc.ncbi.nlm.nih.gov/articles/PMC9844993/
15. Schweighauser https://pmc.ncbi.nlm.nih.gov/articles/PMC9095482/