Abstract
Cofilin-1 protein, which main function is to regulate actin cytoskeleton dynamics, appears to be involved with many steps in the neurotoxicity processes found in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). As the dynamics of actin filaments play a major role in several cellular processes, the primary involvement of cofilin-1 dysfunctions in the pathophysiology of these disorders may be related to a cytoskeleton stress. However, recently cofilin-1 has also been related to other biological processes such as cell death by apoptosis. In both cases, ATP depletion associated with the presence of reactive species and other stressors regulate cofilin-1 by inducing the formation of aggregates composed primarily by actin and cofilin-1, known as cofilin/actin rods. These structures seem to be formed initially as a neuroprotective response to mitochondrial damage; but once the stressor persists they are thought to act as inducers of further impairments and loss of neuronal functions. Therefore, here we provide a brief overview of the current knowledge about the central role of cofilin/actin rods formation, where its dysregulation and malfunction might be the trigger to neurodegeneration.
Keywords: Cofilin-1, cofilin/actin rods, ATP depletion, neurodegeneration, ROS.
Mini-Reviews in Medicinal Chemistry
Title:Cofilin/Actin Rod Formation by Dysregulation of Cofilin-1 Activity as a Central Initial Step in Neurodegeneration
Volume: 14 Issue: 5
Author(s): Patricia Schonhofen, Liana Marengo de Medeiros, Carolina Piletti Chatain, Ivi Juliana Bristot and Fabio Klamt
Affiliation:
Keywords: Cofilin-1, cofilin/actin rods, ATP depletion, neurodegeneration, ROS.
Abstract: Cofilin-1 protein, which main function is to regulate actin cytoskeleton dynamics, appears to be involved with many steps in the neurotoxicity processes found in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). As the dynamics of actin filaments play a major role in several cellular processes, the primary involvement of cofilin-1 dysfunctions in the pathophysiology of these disorders may be related to a cytoskeleton stress. However, recently cofilin-1 has also been related to other biological processes such as cell death by apoptosis. In both cases, ATP depletion associated with the presence of reactive species and other stressors regulate cofilin-1 by inducing the formation of aggregates composed primarily by actin and cofilin-1, known as cofilin/actin rods. These structures seem to be formed initially as a neuroprotective response to mitochondrial damage; but once the stressor persists they are thought to act as inducers of further impairments and loss of neuronal functions. Therefore, here we provide a brief overview of the current knowledge about the central role of cofilin/actin rods formation, where its dysregulation and malfunction might be the trigger to neurodegeneration.
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Schonhofen Patricia, Medeiros de Liana Marengo, Chatain Piletti Carolina, Bristot Juliana Ivi and Klamt Fabio, Cofilin/Actin Rod Formation by Dysregulation of Cofilin-1 Activity as a Central Initial Step in Neurodegeneration, Mini-Reviews in Medicinal Chemistry 2014; 14 (5) . https://dx.doi.org/10.2174/1389557514666140506161458
DOI https://dx.doi.org/10.2174/1389557514666140506161458 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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