東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

The Role of Histone Deacetylase 3 (H...

Janczura, Karolina J.

FindBook

Google Book

Amazon

博客來

The Role of Histone Deacetylase 3 (HDAC3) in Alzheimer's Disease (AD)-Related Pathologies In Vitro and in the Triple Transgenic AD Mouse Model.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The Role of Histone Deacetylase 3 (HDAC3) in Alzheimer's Disease (AD)-Related Pathologies In Vitro and in the Triple Transgenic AD Mouse Model./
作者:	Janczura, Karolina J.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
面頁冊數:	140 p.
附註:	Source: Dissertations Abstracts International, Volume: 80-12, Section: B.
Contained By:	Dissertations Abstracts International80-12B.
標題:	Neurosciences. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13885116
ISBN:	9781392230893

The Role of Histone Deacetylase 3 (HDAC3) in Alzheimer's Disease (AD)-Related Pathologies In Vitro and in the Triple Transgenic AD Mouse Model.
Janczura, Karolina J.

The Role of Histone Deacetylase 3 (HDAC3) in Alzheimer's Disease (AD)-Related Pathologies In Vitro and in the Triple Transgenic AD Mouse Model. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 140 p.

Source: Dissertations Abstracts International, Volume: 80-12, Section: B.

Thesis (Ph.D.)--University of Miami, 2019.

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

Alzheimer's disease (AD) is the leading cause of age-related dementia. Neuropathological hallmarks of AD include brain deposition of β-amyloid (Aβ) plaques and accumulation of both hyperphosphorylated and acetylated tau. Here, we demonstrate that HDAC3 is a negative regulator of AD pathophysiology. RGFP-966, a brain-penetrant and selective HDAC3 inhibitor, or HDAC3 knockdown increases BDNF expression, increases histone H3 and H4 acetylation, decreases tau phosphorylation and tau acetylation at disease-associated sites, reduces β-secretase cleavage of the amyloid precursor protein (APP) and decreases Aβ1-42 accumulation in HEK-293 cells over-expressing APP with the double Swedish mutation (HEK/APPsw). In the triple transgenic AD mouse model (3xTg-AD), repeated administration of 3 and 10 mg/kg of RGFP-966 reverses pathological tau phosphorylation at Thr181, Ser202 and Ser396, increases levels of the Aβ degrading enzyme Neprilysin in the plasma, decreases Aβ1-42 protein levels in the brain and periphery and improves spatial learning and memory. Lastly, we show that HDAC3 activity, Aβ1-42 accumulation and pathological tau acetylation and phosphorylation decrease in response to RGFP-966 in neurons derived from induced pluripotent stem cells (iPSCs) obtained from APOEε4-carrying AD patients. These data indicate that HDAC3 plays an important regulatory role in the expression and regulation of proteins associated with AD pathophysiology, supporting the notion that HDAC3 may be a disease-modifying therapeutic target.

ISBN: 9781392230893Subjects--Topical Terms:

588700
Neurosciences.

The Role of Histone Deacetylase 3 (HDAC3) in Alzheimer's Disease (AD)-Related Pathologies In Vitro and in the Triple Transgenic AD Mouse Model.
LDR:02674nmm a2200325 4500 001 2207301
005 20190916101817.5
008 201008s2019 ||||||||||||||||| ||eng d
020 $a 9781392230893
035 $a (MiAaPQ)AAI13885116
035 $a (MiAaPQ)miami:11886
035 $a AAI13885116
040 $a MiAaPQ $c MiAaPQ
100 1 $a Janczura, Karolina J. $3 3434280
245 1 4 $a The Role of Histone Deacetylase 3 (HDAC3) in Alzheimer's Disease (AD)-Related Pathologies In Vitro and in the Triple Transgenic AD Mouse Model.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2019
300 $a 140 p.
500 $a Source: Dissertations Abstracts International, Volume: 80-12, Section: B.
500 $a Publisher info.: Dissertation/Thesis.
500 $a Advisor: Wahlestedt, Claes.
502 $a Thesis (Ph.D.)--University of Miami, 2019.
506 $a This item must not be sold to any third party vendors.
520 $a Alzheimer's disease (AD) is the leading cause of age-related dementia. Neuropathological hallmarks of AD include brain deposition of β-amyloid (Aβ) plaques and accumulation of both hyperphosphorylated and acetylated tau. Here, we demonstrate that HDAC3 is a negative regulator of AD pathophysiology. RGFP-966, a brain-penetrant and selective HDAC3 inhibitor, or HDAC3 knockdown increases BDNF expression, increases histone H3 and H4 acetylation, decreases tau phosphorylation and tau acetylation at disease-associated sites, reduces β-secretase cleavage of the amyloid precursor protein (APP) and decreases Aβ1-42 accumulation in HEK-293 cells over-expressing APP with the double Swedish mutation (HEK/APPsw). In the triple transgenic AD mouse model (3xTg-AD), repeated administration of 3 and 10 mg/kg of RGFP-966 reverses pathological tau phosphorylation at Thr181, Ser202 and Ser396, increases levels of the Aβ degrading enzyme Neprilysin in the plasma, decreases Aβ1-42 protein levels in the brain and periphery and improves spatial learning and memory. Lastly, we show that HDAC3 activity, Aβ1-42 accumulation and pathological tau acetylation and phosphorylation decrease in response to RGFP-966 in neurons derived from induced pluripotent stem cells (iPSCs) obtained from APOEε4-carrying AD patients. These data indicate that HDAC3 plays an important regulatory role in the expression and regulation of proteins associated with AD pathophysiology, supporting the notion that HDAC3 may be a disease-modifying therapeutic target.
590 $a School code: 0125.
650 4 $a Neurosciences. $3 588700
650 4 $a Pharmacology. $3 634543
690 $a 0317
690 $a 0419
710 2 $a University of Miami. $b Molecular and Cellular Pharmacology (Medicine). $3 3434281
773 0 $t Dissertations Abstracts International $g 80-12B.
790 $a 0125
791 $a Ph.D.
792 $a 2019
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13885116