兰州大学机构库 >化学化工学院
Cyclophilin D Deficiency Rescues Axonal Mitochondrial Transport in Alzheimer's Neurons
Guo, L; Du, H; Yan, SQ(严世强); Wu, XP; McKhann, GM; Chen, JX; Yan, SS; Yan, SS (reprint author), Univ Kansas, Sch Pharm, Dept Pharmacol & Toxicol, Lawrence, KS 66045 USA.
2013-01-31
Source PublicationPLoS One   Impact Factor & Quartile Of Published Year  The Latest Impact Factor & Quartile
ISSN1932-6203
Volume8Issue:1
AbstractNormal axonal mitochondrial transport and function is essential for the maintenance of synaptic function. Abnormal mitochondrial motility and mitochondrial dysfunction within axons are critical for amyloid beta (A beta)-induced synaptic stress and the loss of synapses relevant to the pathogenesis of Alzheimer's disease (AD). However, the mechanisms controlling axonal mitochondrial function and transport alterations in AD remain elusive. Here, we report an unexplored role of cyclophilin D (CypD)-dependent mitochondrial permeability transition pore (mPTP) in A beta-impaired axonal mitochondrial trafficking. Depletion of CypD significantly protects axonal mitochondrial motility and dynamics from A beta toxicity as shown by increased axonal mitochondrial density and distribution and improved bidirectional transport of axonal mitochondria. Notably, blockade of mPTP by genetic deletion of CypD suppresses A beta-mediated activation of the p38 mitogen-activated protein kinase signaling pathway, reverses axonal mitochondrial abnormalities, improves synaptic function, and attenuates loss of synapse, suggesting a role of CypD-dependent signaling in A beta-induced alterations in axonal mitochondrial trafficking. The potential mechanisms of the protective effects of lacking CypD on A beta-induced abnormal mitochondrial transport in axon are increased axonal calcium buffer capability, diminished reactive oxygen species (ROS), and suppressing downstream signal transduction P38 activation. These findings provide new insights into CypD-dependent mitochondrial mPTP and signaling on mitochondrial trafficking in axons and synaptic degeneration in an environment enriched for A beta.
Subject AreaScience & Technology - Other Topics
PublisherPLOS
DOI10.1371/journal.pone.0054914
Publication PlaceSAN FRANCISCO
Indexed BySCIE ; PubMed ; MEDLINE
Language英语
First Inst
Project NumberNational Institute of Aging [R37AG037319, K99AG037716] ; Alzheimer's Association
WOS IDWOS:000314610600051
Funding OrganizationNational Institute of Aging [R37AG037319, K99AG037716]; Alzheimer's Association
SubtypeArticle
PMID 23382999
Department
[Guo, Lan;
Du, Heng;
Yan, Shiqiang;
Yan, Shirley ShiDu] Univ Kansas, Sch Pharm, Dept Pharmacol & Toxicol, Lawrence, KS 66045 USA;
[Guo, Lan;
Du, Heng;
Yan, Shiqiang;
Yan, Shirley ShiDu] Univ Kansas, Sch Pharm, Higuchi Biosci Ctr, Lawrence, KS 66045 USA;
[Yan, Shiqiang] Lanzhou Univ, Coll Chem & Chem Engn, Lanzhou 730000, Gansu, Peoples R China;
[Wu, Xiaoping...更多
Citation statistics
Document Type期刊论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/74780
Collection化学化工学院
Corresponding AuthorYan, SS (reprint author), Univ Kansas, Sch Pharm, Dept Pharmacol & Toxicol, Lawrence, KS 66045 USA.
Recommended Citation
GB/T 7714
Guo, L,Du, H,Yan, SQ,et al. Cyclophilin D Deficiency Rescues Axonal Mitochondrial Transport in Alzheimer's Neurons[J]. PLoS One,2013,8(1).
APA Guo, L.,Du, H.,Yan, SQ.,Wu, XP.,McKhann, GM.,...&Yan, SS .(2013).Cyclophilin D Deficiency Rescues Axonal Mitochondrial Transport in Alzheimer's Neurons.PLoS One,8(1).
MLA Guo, L,et al."Cyclophilin D Deficiency Rescues Axonal Mitochondrial Transport in Alzheimer's Neurons".PLoS One 8.1(2013).
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