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Citations to this article

Blocking the mitochondrial apoptotic pathway preserves motor neuron viability and function in a mouse model of amyotrophic lateral sclerosis
Nichole A. Reyes, … , Eric J. Huang, Scott A. Oakes
Nichole A. Reyes, … , Eric J. Huang, Scott A. Oakes
Published September 20, 2010
Citation Information: J Clin Invest. 2010;120(10):3673-3679. https://doi.org/10.1172/JCI42986.
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Research Article Neuroscience Article has an altmetric score of 1

Blocking the mitochondrial apoptotic pathway preserves motor neuron viability and function in a mouse model of amyotrophic lateral sclerosis

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Abstract

Apoptosis of motor neurons is a well-documented feature in amyotrophic lateral sclerosis (ALS) and related motor neuron diseases (MNDs). However, the role of apoptosis in the pathogenesis of these diseases remains unresolved. One possibility is that the affected motor neurons only succumb to apoptosis once they have exhausted functional capacity. If true, blocking apoptosis should confer no therapeutic benefit. To directly investigate this idea, we tested whether tissue-specific deletion in the mouse CNS of BCL2-associated X protein (BAX) and BCL2-homologous antagonist/killer (BAK), 2 proapoptotic BCL-2 family proteins that together represent an essential gateway to the mitochondrial apoptotic pathway, would protect against motor neuron degeneration. We found that neuronal deletion of Bax and Bak in a mouse model of familial ALS not only halted neuronal loss, but prevented axonal degeneration, symptom onset, weight loss, and paralysis and extended survival. These results show that motor neurons damaged in ALS activate the mitochondrial apoptotic pathway early in the disease process and that apoptotic signaling directly contributes to neuromuscular degeneration and neuronal dysfunction. Hence, inhibiting apoptosis upstream of mitochondrial permeabilization represents a possible therapeutic strategy for preserving functional motor neurons in ALS and other MNDs.

Authors

Nichole A. Reyes, Jill K. Fisher, Kathryn Austgen, Scott VandenBerg, Eric J. Huang, Scott A. Oakes

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Total citations by year

Year: 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 Total
Citations: 4 6 4 6 1 6 1 2 2 1 10 3 6 6 1 59
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2014 (10)

Title and authors Publication Year
ALS Mutation FUS-R521C Causes DNA Damage and RNA Splicing Defects
Haiyan Qiu, Sebum Lee, Yulei Shang, Wen-Yuan Wang, Kin Fai Au, Sherry Kamiya, Sami Barmada, steven finkbeiner, Hansen Lui, Caitlin Carlton, Amy Tang, Michael Oldham, Hejia Wang, James Shorter, Anthony Filiano, Erik Roberson, Warren Tourtellotte, Bin Chen, Li-Huei Tsai, Eric Huang
Journal of Clinical Investigation 2014
Mitochondrial dysfunction in amyotrophic lateral sclerosis - a valid pharmacological target?: Mitochondrial dysfunction in ALS
H Muyderman, T Chen
British Journal of Pharmacology 2014
Role of mitochondria in mutant SOD1 linked amyotrophic lateral sclerosis
W Tan, P Pasinelli, D Trotti
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 2014
Species-dependent neuropathology in transgenic SOD1 pigs
H Yang, G Wang, H Sun, R Shu, T Liu, CE Wang, Z Liu, Y Zhao, B Zhao, Z Ouyang, D Yang, J Huang, Y Zhou, S Li, X Jiang, Z Xiao, XJ Li, L Lai
Cell Research 2014
Glycoursodeoxycholic Acid Reduces Matrix Metalloproteinase-9 and Caspase-9 Activation in a Cellular Model of Superoxide Dismutase-1 Neurodegeneration
AR Vaz, C Cunha, C Gomes, N Schmucki, M Barbosa, D Brites
Molecular Neurobiology 2014
Microglia centered pathogenesis in ALS: insights in cell interconnectivity
D Brites, AR Vaz
Frontiers in cellular neuroscience 2014
ATF3 expression improves motor function in the ALS mouse model by promoting motor neuron survival and retaining muscle innervation
R Seijffers, J Zhang, JC Matthews, A Chen, E Tamrazian, O Babaniyi, M Selig, M Hynynen, CJ Woolf, RH Brown
Proceedings of the National Academy of Sciences 2014
Golgi fragmentation precedes neuromuscular denervation and is associated with endosome abnormalities in SOD1-ALS mouse motor neurons
V Dis, M Kuijpers, ED Haasdijk, E Teuling, SA Oakes, CC Hoogenraad, D Jaarsma
Acta Neuropathologica Communications 2014
Is the risk of motor neuron disease increased or decreased after cancer? An Australian case-control study
A Stoyanov, R Pamphlett
PloS one 2014
Stem Cell Factor-Activated Bone Marrow Ameliorates Amyotrophic Lateral Sclerosis by Promoting Protective Microglial Migration
Terashima T, Kojima H, Urabe H, Yamakawa I, Ogawa N, Kawai H, Chan L, Maegawa H
Journal of Neuroscience Research 2014

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