scholarly journals Role of Presenilin in Mitochondrial Oxidative Stress and Neurodegeneration in Caenorhabditis elegans

Antioxidants ◽  
2018 ◽  
Vol 7 (9) ◽  
pp. 111 ◽  
Author(s):  
Shaarika Sarasija ◽  
Kenneth Norman
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Caenorhabditis Elegans ◽  
Mitochondrial Function ◽  
Calcium Dysregulation ◽  
Mitochondrial Oxidative Stress ◽  
Health Crisis ◽  
Genes Encoding

Neurodegenerative diseases like Alzheimer’s disease (AD) are poised to become a global health crisis, and therefore understanding the mechanisms underlying the pathogenesis is critical for the development of therapeutic strategies. Mutations in genes encoding presenilin (PSEN) occur in most familial Alzheimer’s disease but the role of PSEN in AD is not fully understood. In this review, the potential modes of pathogenesis of AD are discussed, focusing on calcium homeostasis and mitochondrial function. Moreover, research using Caenorhabditis elegans to explore the effects of calcium dysregulation due to presenilin mutations on mitochondrial function, oxidative stress and neurodegeneration is explored.

scholarly journals Role of Presenilin in Mitochondrial Oxidative Stress and Neurodegeneration in Caenorhabditis elegans

2018 ◽  
Author(s):  
Shaarika Sarasija ◽  
Kenneth R. Norman
Keyword(s):  
Oxidative Stress ◽  
Caenorhabditis Elegans ◽  
Global Health ◽  
Mitochondrial Function ◽  
Therapeutic Strategies ◽  
Calcium Dysregulation ◽  
Mitochondrial Oxidative Stress ◽  
Health Crisis ◽  
Genes Encoding

Neurodegenerative diseases like Alzheimer’s disease (AD) are poised to become a global health crisis, and therefore understanding the mechanisms underlying the pathogenesis is critical for the development of therapeutic strategies. Mutations in genes encoding presenilin occur in most familial Alzheimer’s disease but the role of PSEN in AD is not fully understood. In this review, the potential modes of pathogenesis of AD are discussed, focusing on calcium homeostasis and mitochondrial function. Moreover, research using Caenorhabditis elegans to explore the effects of calcium dysregulation due to presenilin mutations on mitochondrial function, oxidative stress and neurodegeneration is explored.

scholarly journals Role of RALBP1 in Oxidative Stress and Mitochondrial Dysfunction in Alzheimer's Disease

2021 ◽  
Author(s):  
Sanjay Awasthi ◽  
Ashly Hindle ◽  
Neha Sawant ◽  
Mathew George ◽  
Murali Vijayan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Sensory Function ◽  
Expression Of Genes

The purpose of our study is to understand the role of the Ralbp1 gene in oxidative stress (OS), mitochondrial dysfunction and cognition in Alzheimer's disease (AD) pathogenesis. The Ralbp1 gene encodes the 76 kDa protein Rlip (aka RLIP76). Previous studies have revealed its role in OS-related cancer. However, Rlip is transcriptionally regulated by EP300, a CREB-binding protein that is important for synaptic plasticity in the brain. Rlip functions as a stress-responsive/protective transporter of glutathione conjugates (GS-E) and xenobiotic toxins. OS causes rapid cellular accumulation of Rlip and its translocation from a tubulin-bound complex to the plasma membrane, mitochondria and nucleus. Therefore, Rlip may play an important role in maintaining cognitive function in the face of OS-related injury. This study is aimed to determine whether Rlip deficiency in mice is associated with AD-like cognitive and mitochondrial dysfunction. Brain tissue obtained from cohorts of wildtype and Rlip+/- mice were analyzed for OS markers, expression of genes that regulate mitochondrial fission/fusion, and synaptic integrity. We also examined mitochondrial ultrastructure in mouse brains obtained from these mice and further analyzed the impact of Rlip deficiency on gene networks of AD, aging, inhibition of stress-activated gene expression, 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 of these mice. Furthermore, we compared the cognitive function of wildtype and Rlip+/- mice. Behavioral, basic motor and sensory function tests in Rlip+/- 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+/- mouse liver. Our results suggest that the Rlip deficiency-associated increase in OS and mitochondrial dysfunction could contribute to the development of OS-related AD processes. Therefore, the restoration of Rlip activity and endogenous cytoprotective mechanisms by pharmacological interventions is a novel approach to protect against AD.

scholarly journals The Causal Role of Lipoxidative Damage in Mitochondrial Bioenergetic Dysfunction Linked to Alzheimer’s Disease Pathology

Life ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 388
Author(s):  
Mariona Jové ◽  
Natàlia Mota-Martorell ◽  
Pascual Torres ◽  
Victoria Ayala ◽  
Manuel Portero-Otin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Entorhinal Cortex ◽  
Brain Region ◽  
Selective Vulnerability ◽  
Mitochondrial Oxidative Stress ◽  
Starting Point ◽  
Molecular Damage

Current shreds of evidence point to the entorhinal cortex (EC) as the origin of the Alzheimer’s disease (AD) pathology in the cerebrum. Compared with other cortical areas, the neurons from this brain region possess an inherent selective vulnerability derived from particular oxidative stress conditions that favor increased mitochondrial molecular damage with early bioenergetic involvement. This alteration of energy metabolism is the starting point for subsequent changes in a multitude of cell mechanisms, leading to neuronal dysfunction and, ultimately, cell death. These events are induced by changes that come with age, creating the substrate for the alteration of several neuronal pathways that will evolve toward neurodegeneration and, consequently, the development of AD pathology. In this context, the present review will focus on description of the biological mechanisms that confer vulnerability specifically to neurons of the entorhinal cortex, the changes induced by the aging process in this brain region, and the alterations at the mitochondrial level as the earliest mechanism for the development of AD pathology. Current findings allow us to propose the existence of an altered allostatic mechanism at the entorhinal cortex whose core is made up of mitochondrial oxidative stress, lipid metabolism, and energy production, and which, in a positive loop, evolves to neurodegeneration, laying the basis for the onset and progression of AD pathology.

scholarly journals Investigating the role of neuronal oxidative stress in early Alzheimer’s disease pathology

2020 ◽  
Vol 16 (S3) ◽  
Author(s):  
Morgan K. Foret ◽  
Sonia Do Carmo ◽  
Lindsay A. Welikovitch ◽  
Chiara Orciani ◽  
A. Claudio Cuello
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Alzheimer’S Disease

The Key Role of Oxidative Stress in Alzheimer's Disease

2007 ◽  
pp. 267-281 ◽  
Author(s):  
Paula I. Moreira ◽  
Akihiko Nunomura ◽  
Kazuhiro Honda ◽  
Gjumrakch Aliev ◽  
Gemma Casadesus ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease

scholarly journals P-glycoprotein (ABCB1) and Oxidative Stress: Focus on Alzheimer’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Giulia Sita ◽  
Patrizia Hrelia ◽  
Andrea Tarozzi ◽  
Fabiana Morroni
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Drug ◽  
Amyloid A ◽  
P Glycoprotein ◽  
And Function ◽  
The Brain ◽  
Brain Homeostasis

ATP-binding cassette (ABC) transporters, in particular P-glycoprotein (encoded by ABCB1), are important and selective elements of the blood-brain barrier (BBB), and they actively contribute to brain homeostasis. Changes in ABCB1 expression and/or function at the BBB may not only alter the expression and function of other molecules at the BBB but also affect brain environment. Over the last decade, a number of reports have shown that ABCB1 actively mediates the transport of beta amyloid (Aβ) peptide. This finding has opened up an entirely new line of research in the field of Alzheimer’s disease (AD). Indeed, despite intense research efforts, AD remains an unsolved pathology and effective therapies are still unavailable. Here, we review the crucial role of ABCB1 in the Aβtransport and how oxidative stress may interfere with this process. A detailed understanding of ABCB1 regulation can provide the basis for improved neuroprotection in AD and also enhanced therapeutic drug delivery to the brain.

scholarly journals Molecular neuropathogenesis of Alzheimer’s disease: an interaction model stressing the central role of oxidative stress

2012 ◽  
Vol 7 (3) ◽  
pp. 287-305 ◽  
Author(s):  
Roberto Rodrigues ◽  
Mark A Smith ◽  
Xinglong Wang ◽  
George Perry ◽  
Hyoung-gon Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Interaction Model
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