Downregulated AEG-1 together with inhibited PI3K/Akt pathway is associated with reduced viability of motor neurons in an ALS model

Molecular and Cellular Neurosciences
Xiang YinHonglin Feng

Abstract

Astrocyte elevated gene-1 (AEG-1) has been reported to regulate the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and is also regulated by it. This study investigated how AEG-1 participates in the survival pathway of motor neurons in amyotrophic lateral sclerosis (ALS). We found reduced levels of AEG-1 in ALS motor neurons, both in vivo and in vitro, compared to wild type controls. Moreover, AEG-1 silencing demonstrated inhibition of the PI3K/Akt pathway and increased cell apoptosis. Additionally, the PI3K/Akt pathway in mSOD1 cells was unresponsive under serum deprivation conditions compared to wtSOD1 cells. These results suggest that AEG-1 deficiency, together with the inhibited PI3K/Akt pathway was associated with decreased viability of ALS motor neurons. However, the mRNA levels of AEG-1 were still lower in mSOD1 cells compared to the control groups, though the signaling pathway was activated by application of a PI3-K activator. This suggests that in ALS motor neurons, some unknown interruption exists in the PI3K/Akt/CREB/AEG-1 feedback loop, thus attenuating the protection by this signaling pathway. Together, these findings support that AEG-1 is a critical factor for cell survival, and the disrupted PI3K/Akt/CREB/AEG-1c...Continue Reading

References

Mar 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·K YeB D Clark
Jun 23, 2000·Archives of Biochemistry and Biophysics·K A O'Leary, C B Kasper
Nov 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·Seok-Geun LeePaul B Fisher
Jul 9, 2008·Amyotrophic Lateral Sclerosis : Official Publication of the World Federation of Neurology Research Group on Motor Neuron Diseases·Stacey A SakowskiEva L Feldman
Dec 26, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Dairín KieranJochen H M Prehn
Apr 27, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Byoung Kwon YooDevanand Sarkar
May 4, 2011·World Journal of Biological Chemistry·Yuwen LiJongsun Park
Nov 5, 2011·Nature Reviews. Neurology·Laura FerraiuoloPamela J Shaw
Feb 14, 2012·Immunopharmacology and Immunotoxicology·Min Su Seo, Eun Mi Choi
Mar 7, 2013·Nature Reviews. Neuroscience·Wim Robberecht, Thomas Philips
Mar 13, 2014·Frontiers in Cellular Neuroscience·Luis B Tovar-Y-RomoRicardo Tapia
Apr 5, 2014·Human Molecular Genetics·Makiko YamashitaMasato Hasegawa

❮ Previous
Next ❯

Citations

Sep 24, 2016·Molecular Neurobiology·Paula PierozanAngela T S Wyse
Jan 25, 2017·International Journal of Molecular Sciences·Irina O ZakharovaNatalia F Avrova
Oct 26, 2018·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Xing Yang, Shaowei Song
May 7, 2019·Fundamental & Clinical Pharmacology·Nadine PetitpainAntoine Coquerel
Apr 4, 2017·Journal of Neuroscience Research·Xiang Yin, Honglin Feng
Dec 13, 2016·Journal of Tissue Engineering and Regenerative Medicine·Flore GouelDavid Devos
May 7, 2020·Frontiers in Neurology·Pamela A McCombeRobert D Henderson
Jan 15, 2021·Brain Sciences·Hyun-Gug JungEun Mi Hwang
Jan 31, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Chunting ZhangHonglin Feng

❮ Previous
Next ❯

Related Concepts

Related Feeds

Amyloid Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive nervous system disease associated with the death of neurons that control voluntary muscles. Discover the latest research on ALS here.

ALS: Genetics

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. ALS is a genetically heterogeneous disorder with several causative genes. Here are the latest discoveries pertaining to the genetics of this disease.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

ALS: Genetics

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating genetic alterations in this genetically heterogeneous disorder.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Carcinoma, Squamous Cell

Basal cell carcinoma is a form of malignant skin cancer found on the head and neck regions and has low rates of metastasis. Discover the latest research on basal cell carcinoma here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

ALS: Pathogenic Mechanisms

Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating pathogenic mechanisms that underlie this genetically heterogeneous disorder.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.