Sandbox Reserved 1105: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 15: | Line 15: | ||
== Disease == | == Disease == | ||
==Type of disease== | ===Type of disease=== | ||
The most known defect related to TTR is the formation of amyloid fibrils, which can engender several diseases such as familial amyloid polyneuropathy (FAP), familial amyloid cardiomyopathy (FAC), and senile systemic amyloidosis (SSA) also called wild-type transthyretin amyloid (WTTA or ATTR)<ref> Faria TQ, Almeida ZL, Cruz PF, Jesus CS, Castanheira P, Brito RM. A look into amyloid formation by transthyretin: aggregation pathway and a novel kinetic model. Phys Chem Chem Phys. 2015 Mar 4;17(11):7255-63. doi: 10.1039/c4cp04549a. PMID:25694367 doi:http://dx.doi.org/10.1039/c4cp04549a </ref>. Another type of disease possibly engendered due to TTR amyloid fibrils is the central nervous system selective amyloidosis (CNSA) including familial oculoleptomeningeal amyloidosis characterized by an eye injury, or meningocerebrovascular amyloidosis if the eye is not affected. <ref> ARTICLE Human brain amyloidoses</ref> | The most known defect related to TTR is the formation of amyloid fibrils, which can engender several diseases such as familial amyloid polyneuropathy (FAP), familial amyloid cardiomyopathy (FAC), and senile systemic amyloidosis (SSA) also called wild-type transthyretin amyloid (WTTA or ATTR)<ref> Faria TQ, Almeida ZL, Cruz PF, Jesus CS, Castanheira P, Brito RM. A look into amyloid formation by transthyretin: aggregation pathway and a novel kinetic model. Phys Chem Chem Phys. 2015 Mar 4;17(11):7255-63. doi: 10.1039/c4cp04549a. PMID:25694367 doi:http://dx.doi.org/10.1039/c4cp04549a </ref>. Another type of disease possibly engendered due to TTR amyloid fibrils is the central nervous system selective amyloidosis (CNSA) including familial oculoleptomeningeal amyloidosis characterized by an eye injury, or meningocerebrovascular amyloidosis if the eye is not affected. <ref> ARTICLE Human brain amyloidoses</ref> | ||
| Line 64: | Line 64: | ||
===Improvements=== | ====Improvements==== | ||
To exploit the TTR inner cavity, DDBR can be ameliorate <ref name="Klabunde">PMID:10742177</ref>. An additional substituent like an aryl ring could be link at DDBR thought a heteroatom or directly via a covalent bond <ref name="Petrassi"/>. | To exploit the TTR inner cavity, DDBR can be ameliorate <ref name="Klabunde">PMID:10742177</ref>. An additional substituent like an aryl ring could be link at DDBR thought a heteroatom or directly via a covalent bond <ref name="Petrassi"/>. | ||
| Line 71: | Line 71: | ||
<ref name="Klabunde">PMID:10742177</ref> | <ref name="Klabunde">PMID:10742177</ref> | ||
===Advantages=== | ====Advantages==== | ||
The substituted DDBR possess numerous advantages. In vivo, at a molar ratio of 1, there is more of 50% of fibril inhibition activity <ref name="Labaudinière"/> | The substituted DDBR possess numerous advantages. In vivo, at a molar ratio of 1, there is more of 50% of fibril inhibition activity <ref name="Labaudinière"/> | ||
