Inhibition of extracellular regulated kinase (ERK)-1/2 signaling pathway in the prevention of ALS: Target inhibitors and influences on neurological dysfunctions

• Published in: European journal of cell biology Vol. 100; no. 7-8; p. 151179
• Main Authors: Sahu, Rakesh, Upadhayay, Shubham, Mehan, Sidharth
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01-09-2021; Elsevier
• Subjects: Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - drug therapy; Apoptosis; Cell Proliferation; Demyelination; ERK-1/2; Humans; MAP Kinase Signaling System; Neurodegeneration; Neuroinflammation; Neurons; Signal Transduction; AMPA; BBB; RNA; AHL; ALS; H2O2; MEK-1/2; Aβ; OPCs; PNS; ADEM; Neurodegeneration; iNOS; FALS; IL; P2 × 7; MS; MAPK; bFGF; USFDA; TDP-43; OLs; ROS; UMN; GABA; SOD-1; NK; C9orf72; NO; TNF-R1; O2; COX-2; ANS; LPSS; APAF-1; CNS; IFN; BCL-2; Demyelination; NMDA; OH; Amyotrophic lateral sclerosis; Neuroinflammation; LMN; ONOO2; SALS; ERK-1/2; TNF-α; DNA; Caspases; NDs; ATP; GTPase; NOX2
• ISSN: 0171-9335; 1618-1298
• DOI: 10.1016/j.ejcb.2021.151179

[Display omitted]
•ERK-1/2 signalling is required for neural cell proliferation, survival, and neurogenesis.•ALS is a motor neuron disease characterized by cortical and spinal motor neuron demyelination.•ERK1/2 overactivation causes neuropathological changes in ALS and other brain diseases.•Inhibiting ERK1/2-mediated pathways may provide neuroprotection in ALS and related neurocomplications.
Cell signal transduction pathways are essential modulators of several physiological and pathological processes in the brain. During overactivation, these signaling processes may lead to disease progression. Abnormal protein kinase activation is associated with several biological dysfunctions that facilitate neurodegeneration under different biological conditions. As a result, these signaling pathways are essential in understanding brain disorders' development or progression. Recent research findings indicate the crucial role of extracellular signal-regulated kinase-1/2 (ERK-1/2) signaling during the neuronal development process. ERK-1/2 is a key component of its mitogen-activated protein kinase (MAPK) group, controlling certain neurological activities by regulating metabolic pathways, cell proliferation, differentiation, and apoptosis. ERK-1/2 also influences neuronal elastic properties, nerve growth, and neurological and cognitive processing during brain injuries. The primary goal of this review is to elucidate the activation of ERK1/2 signaling, which is involved in the development of several ALS-related neuropathological dysfunctions. ALS is a rare neurological disorder category that mainly affects the nerve cells responsible for regulating voluntary muscle activity. ALS is progressive, which means that the symptoms are getting worse over time, and there is no cure for ALS and no effective treatment to avoid or reverse. Genetic abnormalities, oligodendrocyte degradation, glial overactivation, and immune deregulation are associated with ALS progression. Furthermore, the current review also identifies ERK-1/2 signaling inhibitors that can promote neuroprotection and neurotrophic effects against the clinical-pathological presentation of ALS. As a result, in the future, the potential ERK-1/2 signaling inhibitors could be used in the treatment of ALS and related neurocomplications.