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Parkinson’s disease-implicated kinases in the brain; insights into disease pathogenesis

Substantial evidence implicates abnormal protein kinase function in various aspects of Parkinson’s disease (PD) etiology. Elevated phosphorylation of the PD-defining pathological protein, α-synuclein, correlates with its aggregation and toxic accumulation in neurons, whilst genetic missense mutation...

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Autores principales: Dzamko, Nicolas, Zhou, Jinxia, Huang, Yue, Halliday, Glenda M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068290/
https://www.ncbi.nlm.nih.gov/pubmed/25009465
http://dx.doi.org/10.3389/fnmol.2014.00057
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author Dzamko, Nicolas
Zhou, Jinxia
Huang, Yue
Halliday, Glenda M.
author_facet Dzamko, Nicolas
Zhou, Jinxia
Huang, Yue
Halliday, Glenda M.
author_sort Dzamko, Nicolas
collection PubMed
description Substantial evidence implicates abnormal protein kinase function in various aspects of Parkinson’s disease (PD) etiology. Elevated phosphorylation of the PD-defining pathological protein, α-synuclein, correlates with its aggregation and toxic accumulation in neurons, whilst genetic missense mutations in the kinases PTEN-induced putative kinase 1 and leucine-rich repeat kinase 2, increase susceptibility to PD. Experimental evidence also links kinases of the phosphoinositide 3-kinase and mitogen-activated protein kinase signaling pathways, amongst others, to PD. Understanding how the levels or activities of these enzymes or their substrates change in brain tissue in relation to pathological states can provide insight into disease pathogenesis. Moreover, understanding when and where kinase dysfunction occurs is important as modulation of some of these signaling pathways can potentially lead to PD therapeutics. This review will summarize what is currently known in regard to the expression of these PD-implicated kinases in pathological human postmortem brain tissue.
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spelling pubmed-40682902014-07-09 Parkinson’s disease-implicated kinases in the brain; insights into disease pathogenesis Dzamko, Nicolas Zhou, Jinxia Huang, Yue Halliday, Glenda M. Front Mol Neurosci Neuroscience Substantial evidence implicates abnormal protein kinase function in various aspects of Parkinson’s disease (PD) etiology. Elevated phosphorylation of the PD-defining pathological protein, α-synuclein, correlates with its aggregation and toxic accumulation in neurons, whilst genetic missense mutations in the kinases PTEN-induced putative kinase 1 and leucine-rich repeat kinase 2, increase susceptibility to PD. Experimental evidence also links kinases of the phosphoinositide 3-kinase and mitogen-activated protein kinase signaling pathways, amongst others, to PD. Understanding how the levels or activities of these enzymes or their substrates change in brain tissue in relation to pathological states can provide insight into disease pathogenesis. Moreover, understanding when and where kinase dysfunction occurs is important as modulation of some of these signaling pathways can potentially lead to PD therapeutics. This review will summarize what is currently known in regard to the expression of these PD-implicated kinases in pathological human postmortem brain tissue. Frontiers Media S.A. 2014-06-24 /pmc/articles/PMC4068290/ /pubmed/25009465 http://dx.doi.org/10.3389/fnmol.2014.00057 Text en Copyright © 2014 Dzamko, Zhou, Huang and Halliday. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Dzamko, Nicolas
Zhou, Jinxia
Huang, Yue
Halliday, Glenda M.
Parkinson’s disease-implicated kinases in the brain; insights into disease pathogenesis
title Parkinson’s disease-implicated kinases in the brain; insights into disease pathogenesis
title_full Parkinson’s disease-implicated kinases in the brain; insights into disease pathogenesis
title_fullStr Parkinson’s disease-implicated kinases in the brain; insights into disease pathogenesis
title_full_unstemmed Parkinson’s disease-implicated kinases in the brain; insights into disease pathogenesis
title_short Parkinson’s disease-implicated kinases in the brain; insights into disease pathogenesis
title_sort parkinson’s disease-implicated kinases in the brain; insights into disease pathogenesis
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068290/
https://www.ncbi.nlm.nih.gov/pubmed/25009465
http://dx.doi.org/10.3389/fnmol.2014.00057
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