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Alpha-synuclein sequence variants :Secondary structure formation and aggregation

Record Type:	Electronic resources : Monograph/item
Title/Author:	Alpha-synuclein sequence variants :
Reminder of title:	Secondary structure formation and aggregation
Author:	Kessler, Jeffrey Charles.
Description:	89 p.
Notes:	Adviser: Peter T. Lansbury, Jr.
Notes:	Source: Dissertation Abstracts International, Volume: 65-05, Section: B, page: 2398.
Contained By:	Dissertation Abstracts International65-05B.
Subject:	Chemistry, Biochemistry.
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3131881
ISBN:	0496791214

Alpha-synuclein sequence variants :Secondary structure formation and aggregation
Kessler, Jeffrey Charles.

Alpha-synuclein sequence variants :Secondary structure formation and aggregation [electronic resource] - 89 p.

Adviser: Peter T. Lansbury, Jr.

Thesis (Ph.D.)--Harvard University, 2004.

alpha-Synuclein, a highly expressed neuronal protein of unknown function has been linked to Parkinson's Disease (PD) genetically, via three rare point mutations that cause autosomal dominant early-onset PD, and pathologically as the major component of the Lewy body, intraneuronal cytoplasmic aggregates that are the pathological hallmark of PD. As alpha-synuclein oligomerization, but not fibrillization, is accelerated by the disease-associated mutations, and oligomers possess in vitro permeabilizing activity of lipid vesicles, it is postulated that oligomers are the toxic species in PD. The alpha-synuclein primary sequence contains seven 11-mer N-terminal repeats. To determine the effects of the repeats on protein secondary structure and aggregation, two variants, one with two additional (plus2) and one with two fewer (del2) repeats were generated. Loss of repeats favored aggregation and formation of beta-sheet structure; additional repeats had the opposite effect. To investigate the relationship between sequence and the tendency to form secondary structure further, variants with sequence alterations within the repeats designed to favor either alpha-helix or beta-sheet were generated. From these, a variant (AV) with seven alanine to valine changes demonstrated enhanced oligomer formation. One, three, or four of these alanine to valine transitions did not enhance oligomer formation, suggesting that all seven changes may be required. Variants such as AV may prove useful in testing the toxic oligomer hypothesis in cell culture and animal models of PD.

ISBN: 0496791214Subjects--Topical Terms:

226900
Chemistry, Biochemistry.

Alpha-synuclein sequence variants :Secondary structure formation and aggregation
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