NDLI: KU0063794, a Dual mTORC1 and mTORC2 Inhibitor, Reduces Neural Tissue Damage and Locomotor Impairment After Spinal Cord Injury in Mice

Content Provider	Springer Nature Link
Author	Cordaro, Marika Paterniti, Irene Siracusa, Rosalba Impellizzeri, Daniela Esposito, Emanuela Cuzzocrea, Salvatore
Copyright Year	2016
Abstract	Autophagy is an intracellular catabolic mechanism for the degradation of cytoplasmic constituents in the autophagosomal–lysosomal pathway. This mechanism plays an important role in homeostasis and it is defective in certain diseases. Preceding studies have revealed that autophagy is developing as an important moderator of pathological responses associated to spinal cord injury (SCI) and plays a crucial role in secondary injury initiating a progressive degeneration of the spinal cord. Thus, based on this evidence in this study, we used two different selective inhibitors of mTOR activity to explore the functional role of autophagy in an in vivo model of SCI as well as to determine whether the autophagic process is involved in spinal cord tissue damage. We treated animals with a novel synthetic inhibitor temsirolimus and with a dual mTORC1 and mTORC2 inhibitor KU0063794 matched all with the well-known inhibitor of mTOR the rapamycin. Our results demonstrated that mTOR inhibitors could regulate the neuroinflammation associated to SCI and the results that we obtained evidently demonstrated that rapamycin and temsirolimus significantly diminished the expression of iNOS, COX2, GFAP, and re-established nNOS levels, but the administration of KU0063794 is able to blunt the neuroinflammation better than rapamycin and temsirolimus. In addition, neuronal loss and cell mortality in the spinal cord after injury were considerably reduced in the KU0063794-treated mice. Accordingly, taken together our results denote that the administration of KU0063794 produced a neuroprotective function at the lesion site following SCI, representing a novel therapeutic approach after SCI.
Starting Page	2415
Ending Page	2427
Page Count	13
File Format	PDF
ISSN	08937648
Journal	Molecular Neurobiology
Volume Number	54
Issue Number	4
e-ISSN	15591182
Language	English
Publisher	Springer US
Publisher Date	2016-03-10
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	KU0063794 Temsirolimus SCI Autophagy Inflammation Neurosciences Neurobiology Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Neurology Cellular and Molecular Neuroscience

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Autophagy Inducer Rapamycin Reduces Neural Tissue Damage and Locomotor Impairment after Spinal Cord Injury in Mice

Inhibition of NOX2 reduces locomotor impairment, inflammation, and oxidative stress after spinal cord injury

Autophagy Reduces Neuronal Damage and Promotes Locomotor Recovery via Inhibition of Apoptosis After Spinal Cord Injury in Rats

Erratum to: Autophagy Reduces Neuronal Damage and Promotes Locomotor Recovery via Inhibition of Apoptosis after Spinal Cord Injury in Rats

A Comparison of Ku0063794, a Dual mTORC1 and mTORC2 Inhibitor, and Temsirolimus in Preclinical Renal Cell Carcinoma Models

CCL3 contributes to secondary damage after spinal cord injury

A comparison of Ku0063794, a dual mTORC1 and mTORC2 inhibitor, and temsirolimus in preclinical renal cell carcinoma models. PloS one 8: e54918 (2013)

Autophagy Inhibition Favors Survival of Rubrospinal Neurons After Spinal Cord Hemisection

The NAMPT inhibitor FK866 reverts the damage in spinal cord injury

KU0063794, a Dual mTORC1 and mTORC2 Inhibitor, Reduces Neural Tissue Damage and Locomotor Impairment After Spinal Cord Injury in Mice

Similar Documents

Autophagy Inducer Rapamycin Reduces Neural Tissue Damage and Locomotor Impairment after Spinal Cord Injury in Mice

Inhibition of NOX2 reduces locomotor impairment, inflammation, and oxidative stress after spinal cord injury

Autophagy Reduces Neuronal Damage and Promotes Locomotor Recovery via Inhibition of Apoptosis After Spinal Cord Injury in Rats

Erratum to: Autophagy Reduces Neuronal Damage and Promotes Locomotor Recovery via Inhibition of Apoptosis after Spinal Cord Injury in Rats

A Comparison of Ku0063794, a Dual mTORC1 and mTORC2 Inhibitor, and Temsirolimus in Preclinical Renal Cell Carcinoma Models

CCL3 contributes to secondary damage after spinal cord injury

A comparison of Ku0063794, a dual mTORC1 and mTORC2 inhibitor, and temsirolimus in preclinical renal cell carcinoma models. PloS one 8: e54918 (2013)

Autophagy Inhibition Favors Survival of Rubrospinal Neurons After Spinal Cord Hemisection

The NAMPT inhibitor FK866 reverts the damage in spinal cord injury

KU0063794, a Dual mTORC1 and mTORC2 Inhibitor, Reduces Neural Tissue Damage and Locomotor Impairment After Spinal Cord Injury in Mice