| Storage Buffer | PBS pH 7.4 |
| Storage Temperature | -80ºC |
| Shipping Temperature | Dry Ice. Shipping note: Product will be shipped separately from other products purchased in the same order. |
| Purification | Ion-exchange Purified |
| Cite This Product | Human Recombinant Transthyretin (TTR) L55P Variant Monomers (StressMarq Biosciences | Victoria, BC CANADA | Catalog# SPR-451) |
| Certificate of Analysis | Certified >95% pure using SDS-PAGE analysis. |
| Other Relevant Information | For corresponding PFFs, see catalog# SPR-464 |
| Alternative Names | Transthyretin L55P, TTR L55P, ATTR, Amyloid polyneuropathy, Amyloidosis I, Carpal tunnel syndrome 1, CTS, CTS1, HEL111, HsT2651, PALB, Prealbumin, Prealbumin amyloidosis type I, Prealbumin Thyroxine-binding, TBPA, Thyroxine binding prealbumin, TTHY_HUMAN, TTR |
| Research Areas | ALS Disease, Alzheimer's Disease, Blood, Cardiovascular System, Cell Signaling, Lipid and lipoprotein Metabolism, Metabolism, Neurodegeneration, Neuroscience, Parkinson's Disease, Tangles & Tau |
| Cellular Localization | Cytoplasm, Extracellular exosome, Extracellular Region, Lysosome |
| Accession Number | NP_000362.1 |
| Gene ID | 7276 |
| Swiss Prot | P02766 |
| Scientific Background |
The L55P variant of transthyretin (TTR), a tetrameric transport protein for thyroxine and retinol, is one of the most pathogenic mutations linked to hereditary amyloidosis and other neurodegenerative disorders. This single amino acid substitution destabilizes the native tetrameric structure, promoting dissociation into monomers that readily misfold and aggregate into amyloid fibrils under physiological conditions. Unlike wild-type TTR, the L55P variant forms amyloidogenic monomers that serve as precursors to protofilaments and mature fibrils. These aggregates are implicated in transthyretin amyloid polyneuropathy (ATTR-PN), where they deposit in peripheral nerves and disrupt cellular integrity. The monomeric intermediate exhibits altered tertiary structure and increased β-sheet content, facilitating its transition into neurotoxic assemblies. Recent studies reveal that L55P monomers compromise the blood–nerve barrier and trigger neuroinflammatory responses, exacerbating neuronal damage. Their ability to form protofilaments at neutral pH underscores their pathological relevance in vivo, distinguishing them from other TTR variants that require acidic conditions for fibril formation. Understanding the structural dynamics and aggregation pathways of L55P monomers is critical for developing targeted therapies. Stabilizing the tetrameric form or inhibiting monomer misfolding offers promising strategies to mitigate amyloid deposition and neurodegeneration. In summary, TTR L55P variant monomers are potent initiators of amyloid pathology and neurotoxicity, making them key targets in the quest to understand and treat transthyretin-related neurodegenerative diseases. |
| References |
1. Zeldenrust S.R., Benson M.D. (2010). Wiley. pp. 795–815. 2. Westermark P., Sletten K., Johansson B., Cornwell G.G. (1990). Proc. Natl. Acad. Sci. U.S.A. 87(7): 2843–5. 3. Andrade C. (1952). Brain. 75(3): 408–27. 4. Coelho T. (1996). Curr. Opin. Neurol. 9(5): 355–9. 5. Jacobson D.R, et. al. (1997). N. Engl. J. Med. 336(7): 466–73. 6. Li X. (2011). Mol Neurodegener. 6(1):79. 7. Lashuel H.A., Wurth C., Woo L., and Kelly J.W. (1999) Biochem. 38(41): 13560-13573. |
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