Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury (Nat Med, 2009, 15:377-379)

報告日期: 2009/12/11
報告時間: 16:00/16:50
報告學生: 楊正昌
講評老師: 郭余民
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/981211-2.pdf

Amyloid Precursor Protein Secretases as Therapeutic Targets for Traumatic Brain Injury

Nature Medicine 15, 377-379 (2009)

 

Speaker: Cheng-Chang Yang  

Commentator: Yu-Min Kuo Ph. D.

Date: 12-11-2009 

Time: 16:00- 16:50

Place: Room No. 602

 

Abstract:

Traumatic brain injury (TBI) is the leading cause of mortality and disability among young individuals. Globally the incidence of TBI is rising sharply. Several degenerative cascades will occur after injury, including ion imbalance and glutamate releasing, which promoted neuronal damage and death over time. The later status was known as secondary injury, and the apoptotic and inflammatory pathways were activated as part of this process. Previous study indicated traumatic brain injury probably was a risk factor for the Alzheimer’s disease. Under post-mortem examined,  30% of TBI had Ab deposits. Not only Ab accumulation but also the amyloid precursor protein (APP) enzyme responsible for Ab production including BACE-1 and presenilin-1. Several evidences showed that Ab may caused cell death, activated inflammatory pathways and prime proapoptotic pathways for activation by other insults. The APP secretases may involved in secondary injury, based on this reason we made the APP secretases a potential therapeutic target for TBI. This research planned to elucidate the role of APP secretases after traumatic brain injury. This investigation performed TBI by controlled cortical impact (CCI) of left parietal cortex and animals underwent either b- or g-secretase blocking.  The results demonstrated that blocking APP enzymes improved motor and cognitive deficit and reduced cell loss after traumatic brain injury in mice. These studies suggest that modulation of APP secretases may provide new therapeutic targets for the treatment of TBI.

 

References:

Loane DJ, Pocivavsek A, Moussa CE, Thompson R, Matsuoka Y, Faden AI, Rebeck GW, Burns MP. Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury. Nat Med. 2009 15:377-9.

Lenzlinger PM, Morganti-Kossmann MC, Laurer HL, McIntosh TK. The duality of the inflammatory response to traumatic brain injury. Mol Neurobiol. 2001 24:169-81.