“Preconditioning” with latrepirdine, an adenosine 5′-monophosphate-activated protein kinase activator, delays amyotrophic lateral sclerosis progression in SOD1G93A mice

2015 ◽  
Vol 36 (2) ◽  
pp. 1140-1150 ◽  
Author(s):  
Karen S. Coughlan ◽  
Mollie R. Mitchem ◽  
Marion C. Hogg ◽  
Jochen H.M. Prehn
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Protein Kinase ◽  
Sod1g93a Mice ◽  
Lateral Sclerosis

scholarly journals Recent Advances on the Role of GSK3β in the Pathogenesis of Amyotrophic Lateral Sclerosis

2020 ◽  
Vol 10 (10) ◽  
pp. 675
Author(s):  
Hyun-Jun Choi ◽  
Sun Joo Cha ◽  
Jang-Won Lee ◽  
Hyung-Jun Kim ◽  
Kiyoung Kim
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Critical Role ◽  
Glycogen Synthase Kinase 3 ◽  
Motor Neuron Degeneration ◽  
Neuron Degeneration ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disease characterized by progressive motor neuron degeneration. Although several studies on genes involved in ALS have substantially expanded and improved our understanding of ALS pathogenesis, the exact molecular mechanisms underlying this disease remain poorly understood. Glycogen synthase kinase 3 (GSK3) is a multifunctional serine/threonine-protein kinase that plays a critical role in the regulation of various cellular signaling pathways. Dysregulation of GSK3β activity in neuronal cells has been implicated in the pathogenesis of neurodegenerative diseases. Previous research indicates that GSK3β inactivation plays a neuroprotective role in ALS pathogenesis. GSK3β activity shows an increase in various ALS models and patients. Furthermore, GSK3β inhibition can suppress the defective phenotypes caused by SOD, TDP-43, and FUS expression in various models. This review focuses on the most recent studies related to the therapeutic effect of GSK3β in ALS and provides an overview of how the dysfunction of GSK3β activity contributes to ALS pathogenesis.

scholarly journals Mitogen-Activated Protein Kinase Pathway in Amyotrophic Lateral Sclerosis

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 969
Author(s):  
TG Sahana ◽  
Ke Zhang
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Protein Kinase ◽  
Mapk Pathway ◽  
Signal Transduction Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Spinal Cord Tissue ◽  
Disease Manifestation ◽  
Drug Candidates ◽  
Mitogen Activated Protein ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis is a fatal motor neuron degenerative disease. Multiple genetic and non-genetic risk factors are associated with disease pathogenesis, and several cellular processes, including protein homeostasis, RNA metabolism, vesicle transport, etc., are severely impaired in ALS conditions. Despite the heterogeneity of the disease manifestation and progression, ALS patients show protein aggregates in the motor cortex and spinal cord tissue, which is believed to be at least partially caused by aberrant phase separation and the formation of persistent stress granules. Consistent with this notion, many studies have implicated cellular stress, such as ER stress, DNA damage, oxidative stress, and growth factor depletion, in ALS conditions. The mitogen-activated protein kinase (MAPK) pathway is a fundamental mitogen/stress-activated signal transduction pathway that regulates cell proliferation, differentiation, survival, and death. Here we summarize the fundamental role of MAPK in physiology and ALS pathogenesis. We also discuss pharmacological inhibitors targeting this pathway tested in pre-clinical models, suggesting their role as potential drug candidates.

scholarly journals Protein Kinase CK-1 Inhibitors As New Potential Drugs for Amyotrophic Lateral Sclerosis

2014 ◽  
Vol 57 (6) ◽  
pp. 2755-2772 ◽  
Author(s):  
Irene G. Salado ◽  
Miriam Redondo ◽  
Murilo L. Bello ◽  
Concepción Perez ◽  
Nicole F. Liachko ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Protein Kinase ◽  
Lateral Sclerosis
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