NDLI: Rho Kinase Pathway Alterations in the Brain and Leukocytes in Huntington’s Disease

Content Provider	Springer Nature Link
Author	Narayanan, K. Lakshmi Chopra, Vanita Rosas, H. Diana Malarick, Keith Hersch, Steven
Copyright Year	2015
Abstract	Huntington’s disease (HD) is a fatal neurodegenerative disease caused by an expanded polyglutamine tract in the huntingtin gene. Therapeutic approaches targeting mutant huntingtin (mtHtt) or its downstream toxic consequences are under development, including Rho kinase pathway inhibition. We investigated the messenger RNA (mRNA) expression of Rho kinase pathway genes, including RhoA (Ras homolog family member A), ROCK1 (Rho-associated kinase1), PRK2 (protein kinase C-related protein kinase 2), Profilin1, cofilin1, MYPT1 (myosin phosphatase target subunit 1), and LIMK1 (LIM domain kinase 1) in HD human blood leukocytes, postmortem brain, and in R6/2 HD mouse brain tissue using qPCR. RhoA, ROCK1, PRK2, Profilin1, cofilin1, and MYPT1 were significantly increased in HD blood compared to controls. In frontal cortex of HD postmortem brain tissue, the expression of RhoA, ROCK1, PRK2, Profilin1, and MYPT1 were also significantly increased. In the brain from 4-week-old R6/2 mice, the expression of Rock1, Prk2, Cofilin1, and MYPT1 was significantly increased while RhoA, Rock1, Profilin1, Cofilin1, and Mypt1 were increased and Limk1 mRNA decreased in 13-week-old R6/2 mice. Western blot analysis using human postmortem tissues for ROCK1 and Profilin1 demonstrated significantly increased protein levels, which correlated with the mRNA increases. Collectively, we have shown the panel of Rho kinase pathway genes to be highly altered in human HD blood, postmortem brain tissue, and in R6/2 mice. These studies confirm that HD upregulates the Rho kinase pathway and identifies mRNAs that could serve as peripheral markers in HD patients and translational markers in HD mouse models.
Starting Page	2132
Ending Page	2140
Page Count	9
File Format	PDF
ISSN	08937648
Journal	Molecular Neurobiology
Volume Number	53
Issue Number	4
e-ISSN	15591182
Language	English
Publisher	Springer US
Publisher Date	2015-05-05
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Huntington’s disease Rho kinase pathway mRNA expression Biomarker 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

Rho Kinase Pathway Alterations in the Brain and Leukocytes in Huntington’s Disease

Rho Kinase Pathway Alterations in the Brain and Leukocytes in Huntington’s Disease

Huntington’s Disease: Relationship Between Phenotype and Genotype

Altered Expression of the Long Noncoding RNA NEAT1 in Huntington’s Disease

DNA Repair Mechanisms in Huntington’s Disease

Huntington’s Disease and Group I Metabotropic Glutamate Receptors

Targeting Glial Cells to Elucidate the Pathogenesis of Huntington’s Disease

The early cellular pathology of Huntington’s disease

Brain Insulin Dysregulation: Implication for Neurological and Neuropsychiatric Disorders

Rho Kinase Pathway Alterations in the Brain and Leukocytes in Huntington’s Disease

Similar Documents

Rho Kinase Pathway Alterations in the Brain and Leukocytes in Huntington’s Disease

Rho Kinase Pathway Alterations in the Brain and Leukocytes in Huntington’s Disease

Huntington’s Disease: Relationship Between Phenotype and Genotype

Altered Expression of the Long Noncoding RNA NEAT1 in Huntington’s Disease

DNA Repair Mechanisms in Huntington’s Disease

Huntington’s Disease and Group I Metabotropic Glutamate Receptors

Targeting Glial Cells to Elucidate the Pathogenesis of Huntington’s Disease

The early cellular pathology of Huntington’s disease

Brain Insulin Dysregulation: Implication for Neurological and Neuropsychiatric Disorders

Rho Kinase Pathway Alterations in the Brain and Leukocytes in Huntington’s Disease