RALBP1 in Oxidative Stress and Mitochondrial Dysfunction in Alzheimer’s Disease

The purpose of our study is to understand the role of the <i>RALBP1</i> gene in oxidative stress (OS), mitochondrial dysfunction and cognition in Alzheimer’s disease (AD) pathogenesis. The <i>RALPB1</i> gene encodes the 76 kDa protein RLIP76 (Rlip). Rlip functions as a stress...

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Autores principales:	Sanjay Awasthi, Ashly Hindle, Neha A. Sawant, Mathew George, Murali Vijayan, Sudhir Kshirsagar, Hallie Morton, Lloyd E. Bunquin, Philip T. Palade, J. Josh Lawrence, Hafiz Khan, Chhanda Bose, P. Hemachandra Reddy, Sharda P. Singh
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Alzheimer’s disease mitochondria mitophagy mitochondrial biogenesis synaptic proteins Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e190e49133eb4f918fe34b7c91dd8f50
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spelling	oai:doaj.org-article:e190e49133eb4f918fe34b7c91dd8f502021-11-25T17:11:37ZRALBP1 in Oxidative Stress and Mitochondrial Dysfunction in Alzheimer’s Disease10.3390/cells101131132073-4409https://doaj.org/article/e190e49133eb4f918fe34b7c91dd8f502021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3113https://doaj.org/toc/2073-4409The purpose of our study is to understand the role of the <i>RALBP1</i> gene in oxidative stress (OS), mitochondrial dysfunction and cognition in Alzheimer’s disease (AD) pathogenesis. The <i>RALPB1</i> gene encodes the 76 kDa protein RLIP76 (Rlip). Rlip functions as a stress-responsive/protective transporter of glutathione conjugates (GS-E) and xenobiotic toxins. We hypothesized that Rlip may play an important role in maintaining cognitive function. The aim of this study is to determine whether Rlip deficiency in mice is associated with AD-like cognitive and mitochondrial dysfunction. Brain tissue obtained from cohorts of wildtype (WT) and Rlip<sup>+/−</sup> mice were analyzed for OS markers, expression of genes that regulate mitochondrial fission/fusion, and synaptic integrity. We also examined mitochondrial ultrastructure in brains obtained from these mice and further analyzed the impact of Rlip deficiency on gene networks of AD, aging, stress response, mitochondrial function, and CREB signaling. Our studies revealed a significant increase in the levels of OS markers and alterations in the expression of genes and proteins involved in mitochondrial biogenesis, dynamics and synapses in brain tissues from these mice. Furthermore, we compared the cognitive function of WT and Rlip<sup>+/−</sup> mice. Behavioral, basic motor and sensory function tests in Rlip<sup>+/−</sup> mice revealed cognitive decline, similar to AD. Gene network analysis indicated dysregulation of stress-activated gene expression, mitochondrial function and CREB signaling genes in the Rlip<sup>+/−</sup> mouse brain. Our results suggest that Rlip deficiency-associated increases in OS and mitochondrial dysfunction could contribute to the development or progression of OS-related AD processes.Sanjay AwasthiAshly HindleNeha A. SawantMathew GeorgeMurali VijayanSudhir KshirsagarHallie MortonLloyd E. BunquinPhilip T. PaladeJ. Josh LawrenceHafiz KhanChhanda BoseP. Hemachandra ReddySharda P. SinghMDPI AGarticleAlzheimer’s diseasemitochondriamitophagymitochondrial biogenesissynaptic proteinsBiology (General)QH301-705.5ENCells, Vol 10, Iss 3113, p 3113 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alzheimer’s disease mitochondria mitophagy mitochondrial biogenesis synaptic proteins Biology (General) QH301-705.5
spellingShingle	Alzheimer’s disease mitochondria mitophagy mitochondrial biogenesis synaptic proteins Biology (General) QH301-705.5 Sanjay Awasthi Ashly Hindle Neha A. Sawant Mathew George Murali Vijayan Sudhir Kshirsagar Hallie Morton Lloyd E. Bunquin Philip T. Palade J. Josh Lawrence Hafiz Khan Chhanda Bose P. Hemachandra Reddy Sharda P. Singh RALBP1 in Oxidative Stress and Mitochondrial Dysfunction in Alzheimer’s Disease
description	The purpose of our study is to understand the role of the <i>RALBP1</i> gene in oxidative stress (OS), mitochondrial dysfunction and cognition in Alzheimer’s disease (AD) pathogenesis. The <i>RALPB1</i> gene encodes the 76 kDa protein RLIP76 (Rlip). Rlip functions as a stress-responsive/protective transporter of glutathione conjugates (GS-E) and xenobiotic toxins. We hypothesized that Rlip may play an important role in maintaining cognitive function. The aim of this study is to determine whether Rlip deficiency in mice is associated with AD-like cognitive and mitochondrial dysfunction. Brain tissue obtained from cohorts of wildtype (WT) and Rlip<sup>+/−</sup> mice were analyzed for OS markers, expression of genes that regulate mitochondrial fission/fusion, and synaptic integrity. We also examined mitochondrial ultrastructure in brains obtained from these mice and further analyzed the impact of Rlip deficiency on gene networks of AD, aging, stress response, mitochondrial function, and CREB signaling. Our studies revealed a significant increase in the levels of OS markers and alterations in the expression of genes and proteins involved in mitochondrial biogenesis, dynamics and synapses in brain tissues from these mice. Furthermore, we compared the cognitive function of WT and Rlip<sup>+/−</sup> mice. Behavioral, basic motor and sensory function tests in Rlip<sup>+/−</sup> mice revealed cognitive decline, similar to AD. Gene network analysis indicated dysregulation of stress-activated gene expression, mitochondrial function and CREB signaling genes in the Rlip<sup>+/−</sup> mouse brain. Our results suggest that Rlip deficiency-associated increases in OS and mitochondrial dysfunction could contribute to the development or progression of OS-related AD processes.
format	article
author	Sanjay Awasthi Ashly Hindle Neha A. Sawant Mathew George Murali Vijayan Sudhir Kshirsagar Hallie Morton Lloyd E. Bunquin Philip T. Palade J. Josh Lawrence Hafiz Khan Chhanda Bose P. Hemachandra Reddy Sharda P. Singh
author_facet	Sanjay Awasthi Ashly Hindle Neha A. Sawant Mathew George Murali Vijayan Sudhir Kshirsagar Hallie Morton Lloyd E. Bunquin Philip T. Palade J. Josh Lawrence Hafiz Khan Chhanda Bose P. Hemachandra Reddy Sharda P. Singh
author_sort	Sanjay Awasthi
title	RALBP1 in Oxidative Stress and Mitochondrial Dysfunction in Alzheimer’s Disease
title_short	RALBP1 in Oxidative Stress and Mitochondrial Dysfunction in Alzheimer’s Disease
title_full	RALBP1 in Oxidative Stress and Mitochondrial Dysfunction in Alzheimer’s Disease
title_fullStr	RALBP1 in Oxidative Stress and Mitochondrial Dysfunction in Alzheimer’s Disease
title_full_unstemmed	RALBP1 in Oxidative Stress and Mitochondrial Dysfunction in Alzheimer’s Disease
title_sort	ralbp1 in oxidative stress and mitochondrial dysfunction in alzheimer’s disease
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e190e49133eb4f918fe34b7c91dd8f50
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RALBP1 in Oxidative Stress and Mitochondrial Dysfunction in Alzheimer’s Disease

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