![]() We used an unbiased D-amino acid substitution strategy to determine structure-assembly relationships of 76 different Aβ40 and Aβ42 peptides.Īmyloid β-protein (Aβ) assembly is hypothesized to be a seminal neuropathologic event in Alzheimer’s disease (AD). We determined the effects of the substitutions on peptide oligomerization, secondary structure dynamics, fibril assembly dynamics, and fibril morphology. Description With its unique design, the UNFOLDER Platinum Series handpiece provides precise, controlled delivery. the unfolder platinum 1 series implantation system designed for micro-implantation procedures abbott a promise for life n u f 1 a c c e s s o r i e s a t h e p l a i n m u l m 1 s h t r d o h y i n s i y s r u l m h 1 m 1 s p h l y y 1 r t e p l e a i nl hu a e 1 i n n n n n n n s l e p r n t h e p l a. Our experiments revealed that the assembly of Aβ42 was more sensitive to chiral substitutions than was Aβ40 assembly. Santa Ana, CA-Advanced Medical Optics Inc.'s (AMO) Silver Series Unfolder can be used successfully with the Tecnis and CeeOn IOLs, which the company recently acquired from Pfizer Ophthalmics. Substitutions at identical positions in the two peptides often, but not always, produced the same effects on assembly. Sites causing substantial effects in both Aβ40 and Aβ42 include His14, Gln15, Ala30, Ile31, Met35, and Val36. Sites whose effects were unique to Aβ40 include Lys16, Leu17, and Asn 27, whereas sites unique to Aβ42 include Phe20 and Ala21. Intraoperative cracking of the AMO Phacoflex-II Silicone (SI-40NB) intraocular lens while implanting with the Unfolder silver series system using hydroxypropylmethylcellulose. Surgial Technique The 2 flaps of the Silver or Sapphire Series cartridge are closed. These sites may be appropriate targets for therapeutic agents that inhibit or potentiate, respectively, these effects.Īlzheimer’s disease (AD) is the most common cause of late-life dementia 1 and recently has been identified as the 6th leading cause of death in the U.S. We describe the use of the Unfolder Silver/Sapphire Series implantation system (Advanced Medical Optics, Inc.), designed to implant the SI40 or Sensar intraocular lens (IOL), to insert a CTR into the capsular bag. Thus, there is a compelling need for the development of approaches to prevent, ameliorate, or cure this tragic disorder. A predominant working hypothesis of disease causation posits that oligomeric forms of the amyloid β-protein (Aβ) are key neurotoxic agents 3. If so, then therapeutic drug development requires appropriate targeting of these assemblies. A variety of targeting strategies have been executed, including those directed against the enzymes responsible for Aβ production (β-secretase and γ-secretase) 4 or immunogenic sites on monomeric, oligomeric, and fibrillar forms of Aβ 5. Unfortunately, none have resulted in an FDA-approved therapeutic agent 6.Īβ exists in humans predominantly in two forms, Aβ40 and Aβ42, that are 40 or 42 amino acid residues in length, respectively 4. Aβ42 appears to be the most disease-relevant peptide 7– 9.
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