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Clusterin Modulates Amyloid-β Peptide Levels Without Affecting Their Production.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Clusterin Modulates Amyloid-β Peptide Levels Without Affecting Their Production./
Author:	Eng, James.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2020,
Description:	56 p.
Notes:	Source: Masters Abstracts International, Volume: 82-05.
Contained By:	Masters Abstracts International82-05.
Subject:	Pharmacology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28266967
ISBN:	9798691247293

Clusterin Modulates Amyloid-β Peptide Levels Without Affecting Their Production.
Eng, James.

Clusterin Modulates Amyloid-β Peptide Levels Without Affecting Their Production. - Ann Arbor : ProQuest Dissertations & Theses, 2020 - 56 p.

Source: Masters Abstracts International, Volume: 82-05.

Thesis (M.S.)--McGill University (Canada), 2020.

This item must not be sold to any third party vendors.

Alzheimer disease (AD) is the world's most common form of dementia (43.8 million affected as of 2016) and, due to rapidly aging populations, the incidence and socioeconomic burden of this disease is expected to dramatically increase by 2050 (projection is 100 million affected). A critical event in the pathogenesis of AD is the accumulation of amyloid-beta (Aβ) peptides as toxic Aβ oligomers in the brain which ultimately lead to neuronal damage and synaptic loss. Increased Aβ peptide accumulation can occur through two possible routes: (1) the over production of Aβ from the enzymatic cleavage of amyloid precursor protein (APP) or (2) a decrease in the degradation and clearance of Aβ peptides. Clusterin is an extracellular chaperone linked to sporadic AD through genome-wide association studies, but its role in the pathogenesis of AD remains unresolved. Therefore, my thesis sought to examine the effects of clusterin on Aβ peptide production versus degradation. The clusterin overexpression experiments resulted in increased Aβ peptide levels, an effect that was independent of Aβ production since clusterin failed to modulate the beta- or gamma-secretase enzymes that sequentially cleave APP. Thus, the data indicate that clusterin likely modulates the degradation and clearance of Aβ peptides. Since clusterin is up-regulated in AD, future studies are needed to determine the precise mechanism by which clusterin can increase Aβ peptide levels. If the negative impact of clusterin on amyloid degradation and clearance can be circumvented, this provides a new therapeutic strategy to combat the pathogenesis of AD.

ISBN: 9798691247293Subjects--Topical Terms:

634543
Pharmacology.
Subjects--Index Terms:

Clusterin overexpression

Clusterin Modulates Amyloid-β Peptide Levels Without Affecting Their Production.
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245 1 0 $a Clusterin Modulates Amyloid-β Peptide Levels Without Affecting Their Production.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2020
300 $a 56 p.
500 $a Source: Masters Abstracts International, Volume: 82-05.
500 $a Advisor: Multhaup, Gerhard.
502 $a Thesis (M.S.)--McGill University (Canada), 2020.
506 $a This item must not be sold to any third party vendors.
520 $a Alzheimer disease (AD) is the world's most common form of dementia (43.8 million affected as of 2016) and, due to rapidly aging populations, the incidence and socioeconomic burden of this disease is expected to dramatically increase by 2050 (projection is 100 million affected). A critical event in the pathogenesis of AD is the accumulation of amyloid-beta (Aβ) peptides as toxic Aβ oligomers in the brain which ultimately lead to neuronal damage and synaptic loss. Increased Aβ peptide accumulation can occur through two possible routes: (1) the over production of Aβ from the enzymatic cleavage of amyloid precursor protein (APP) or (2) a decrease in the degradation and clearance of Aβ peptides. Clusterin is an extracellular chaperone linked to sporadic AD through genome-wide association studies, but its role in the pathogenesis of AD remains unresolved. Therefore, my thesis sought to examine the effects of clusterin on Aβ peptide production versus degradation. The clusterin overexpression experiments resulted in increased Aβ peptide levels, an effect that was independent of Aβ production since clusterin failed to modulate the beta- or gamma-secretase enzymes that sequentially cleave APP. Thus, the data indicate that clusterin likely modulates the degradation and clearance of Aβ peptides. Since clusterin is up-regulated in AD, future studies are needed to determine the precise mechanism by which clusterin can increase Aβ peptide levels. If the negative impact of clusterin on amyloid degradation and clearance can be circumvented, this provides a new therapeutic strategy to combat the pathogenesis of AD.
520 $a La maladie d'Alzheimer (MA) est la forme de demence la plus repandue dans le monde (43,8 millions de personnes atteintes en 2016) et en consequence du vieillissement rapide de la population, l'incidence et l'impact socioeconomique de cette maladie devraient augmenter considerablement d'ici 2050 (100 millions de personnes seraient touchees). L'accumulation de peptides d'amyloide beta (Aβ) dans le cerveau, surtout les oligomeres de Aβ toxiques, entrainent des lesions neuronales ainsi q'une perte synaptique. Ceci est un evenement critique dans la pathogenese de la MA. L'accumulation accrue de peptides Aβ peut se produire de deux manieres: (1) la surproduction de Aβ a partir du clivage enzymatique de la proteine precurseur de l'amyloide (APP) ou (2) une diminution de la degradation et de la clairance des peptides Aβ. La clusterine est un chaperon extracellulaire lie a la MA sporadique par le biais d'etudes d'association pangenomique. Cependant,son role dans la pathogenese de la MA n'est pas encore resolu. Par consequent, ma these visait a examiner les effets de la clusterine sur la production de peptides Aβ par rapport a la degradation. Les experiences de surexpression de la clusterine ont entraine une augmentation des niveaux de peptides Aβ, un effet independant de la production de Aβ comme la clusterine n'a pas module les enzymes beta ou gamma-secretase qui clivent en sequence l'APP. Ainsi, les donnees indiquent que la clusterine module probablement la degradation et la clairance des peptides Aβ. Plus d'etudes sont necessaires pour determiner le mecanisme precis par lequel la clusterine peut augmenter les niveaux de peptides Aβ. Si l'impact negatif de la clusterine sur la degradation et la clairance de l'amyloide peut etre contourne, cela fournirait une nouvelle strategie therapeutique pour lutter contre la pathogenese de la MA.
590 $a School code: 0781.
650 4 $a Pharmacology. $3 634543
650 4 $a Epidemiology. $3 568544
653 $a Clusterin overexpression
653 $a Amyloid-beta peptides
653 $a Clusterin role in Alzheimer disease
690 $a 0766
690 $a 0419
710 2 $a McGill University (Canada). $3 1018122
773 0 $t Masters Abstracts International $g 82-05.
790 $a 0781
791 $a M.S.
792 $a 2020
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28266967