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 neuropathology on brain-...

Carlos, Anthony J.

FindBook

Google Book

Amazon

博客來

The role of neuropathology on brain-derived neurotrophic factor endosomal transport: Underlying biological mechanisms of Neurological Disorders.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The role of neuropathology on brain-derived neurotrophic factor endosomal transport: Underlying biological mechanisms of Neurological Disorders./
作者:	Carlos, Anthony J.
面頁冊數:	118 p.
附註:	Source: Dissertation Abstracts International, Volume: 77-08(E), Section: B.
Contained By:	Dissertation Abstracts International77-08B(E).
標題:	Neurosciences. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10046751
ISBN:	9781339563701

The role of neuropathology on brain-derived neurotrophic factor endosomal transport: Underlying biological mechanisms of Neurological Disorders.
Carlos, Anthony J.

The role of neuropathology on brain-derived neurotrophic factor endosomal transport: Underlying biological mechanisms of Neurological Disorders. - 118 p.

Source: Dissertation Abstracts International, Volume: 77-08(E), Section: B.

Thesis (Ph.D.)--University of California, Irvine, 2016.

Accumulation of Abeta and chronic inflammation are hallmark neuropathological findings that define Alzheimer's Disease. Both Abeta and pro-inflammatory cytokines have been linked to poor cognitive function, likely owing to impaired neuronal signaling and attenuation of neurotrophic factor signaling. BDNF endosomal transport is a key signaling system facilitating many aspects of healthy brain function and synaptic plasticity. Furthermore, proper intracellular transport via the endosomal trafficking system is crucial to maintain steady-state BDNF signaling. This dissertation focuses on how Abeta and IL-1beta act both synergistically and distinctly to induce a state of abnormal neuronal endosome transport of BDNF. Utilizing a specialized microfluidic isolation chamber for in vitro primary neuronal cultures, we demonstrate that Abeta oligomers compromise BDNF retrograde transport by impairing endosomal transport rate, resulting in impaired downstream signaling driven by BDNF. In a similar fashion, we show that IL-1beta also attenuates BDNF endosomal trafficking flux and the dispersion of BDNF signaling endosomes throughout neurite networks in cultures. Distinct from Abeta however, the mechanism for IL-1beta-induced deficits to BDNF endosomal signaling did not arise from impaired rate of transport of the BDNF-TrkB receptor complex. Rather, IL-1beta may be associated with a Ub-dependent presynaptic sorting deficit. Our data suggests that ubiquitin C-terminal hydrolase L1 (UCH-L1), a deubiquitinating enzyme that functions to regulate cellular ubiquitin, mediates these trafficking deficits, since the irregularity in BDNF trafficking can be reversed by increasing cellular UCH-L1 levels. UCH-L1 is important for regulating neurotrophin receptor sorting and supporting retrograde transport. Thus, this work supports the idea that in AD or other neurological conditions where chronic inflammation is present, down-regulated UCH-L1 may drive BDNF trafficking deficits, compromising synaptic plasticity and neuronal survival. Collectively, the data indicate that both Abeta and IL-1beta distinctly contribute to BDNF trafficking deficits, and that Abeta-induced deficits can be rescued in vitro by UCH-L1 overexpression.

ISBN: 9781339563701Subjects--Topical Terms:

588700
Neurosciences.

The role of neuropathology on brain-derived neurotrophic factor endosomal transport: Underlying biological mechanisms of Neurological Disorders.
LDR:03187nmm a2200277 4500 001 2074298
005 20160926125806.5
008 170521s2016 ||||||||||||||||| ||eng d
020 $a 9781339563701
035 $a (MiAaPQ)AAI10046751
035 $a AAI10046751
040 $a MiAaPQ $c MiAaPQ
100 1 $a Carlos, Anthony J. $3 3189590
245 1 4 $a The role of neuropathology on brain-derived neurotrophic factor endosomal transport: Underlying biological mechanisms of Neurological Disorders.
300 $a 118 p.
500 $a Source: Dissertation Abstracts International, Volume: 77-08(E), Section: B.
500 $a Adviser: Carl W. Cotman.
502 $a Thesis (Ph.D.)--University of California, Irvine, 2016.
520 $a Accumulation of Abeta and chronic inflammation are hallmark neuropathological findings that define Alzheimer's Disease. Both Abeta and pro-inflammatory cytokines have been linked to poor cognitive function, likely owing to impaired neuronal signaling and attenuation of neurotrophic factor signaling. BDNF endosomal transport is a key signaling system facilitating many aspects of healthy brain function and synaptic plasticity. Furthermore, proper intracellular transport via the endosomal trafficking system is crucial to maintain steady-state BDNF signaling. This dissertation focuses on how Abeta and IL-1beta act both synergistically and distinctly to induce a state of abnormal neuronal endosome transport of BDNF. Utilizing a specialized microfluidic isolation chamber for in vitro primary neuronal cultures, we demonstrate that Abeta oligomers compromise BDNF retrograde transport by impairing endosomal transport rate, resulting in impaired downstream signaling driven by BDNF. In a similar fashion, we show that IL-1beta also attenuates BDNF endosomal trafficking flux and the dispersion of BDNF signaling endosomes throughout neurite networks in cultures. Distinct from Abeta however, the mechanism for IL-1beta-induced deficits to BDNF endosomal signaling did not arise from impaired rate of transport of the BDNF-TrkB receptor complex. Rather, IL-1beta may be associated with a Ub-dependent presynaptic sorting deficit. Our data suggests that ubiquitin C-terminal hydrolase L1 (UCH-L1), a deubiquitinating enzyme that functions to regulate cellular ubiquitin, mediates these trafficking deficits, since the irregularity in BDNF trafficking can be reversed by increasing cellular UCH-L1 levels. UCH-L1 is important for regulating neurotrophin receptor sorting and supporting retrograde transport. Thus, this work supports the idea that in AD or other neurological conditions where chronic inflammation is present, down-regulated UCH-L1 may drive BDNF trafficking deficits, compromising synaptic plasticity and neuronal survival. Collectively, the data indicate that both Abeta and IL-1beta distinctly contribute to BDNF trafficking deficits, and that Abeta-induced deficits can be rescued in vitro by UCH-L1 overexpression.
590 $a School code: 0030.
650 4 $a Neurosciences. $3 588700
650 4 $a Pathology. $3 643180
690 $a 0317
690 $a 0571
710 2 $a University of California, Irvine. $b Biological Sciences - Ph.D.. $3 3189591
773 0 $t Dissertation Abstracts International $g 77-08B(E).
790 $a 0030
791 $a Ph.D.
792 $a 2016
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10046751