The role of caspases in Parkinson’s Disease pathogenesis: a brief look at the mitochondrial pathway

2.50
Hdl Handle:
http://hdl.handle.net/10547/565834
Title:
The role of caspases in Parkinson’s Disease pathogenesis: a brief look at the mitochondrial pathway
Authors:
Chaudhry, Zahara Latif; Ahmed, Bushra Y.
Abstract:
Parkinson’s disease (PD) is a neurodegenerative disorder characterised by tremor, rigidity, Bradykinesia and reduced facial expression. Development of PD is considered to be the result of deficiency of the neurotransmitter dopamine, which is due to death of Dopamine-Containing Neurons (DCNs) that produce dopamine in the pars compacta region of the substantia nigra. Although the concentrated efforts of the scientific community over the last decades, the etiology of the death of DCN is yet to be understood. Oxidative stress has been considered as one of the causes of defects in the mitochondria leading to the dopaminergic cell damage [1]. Levodopa therapy is a well-known treatment for the symptoms of PD, however long term use of L-dopa causes side effects including further enhancement of oxidative stress [2]. The elevated levels of Reactive Oxidative Species (ROS) such as hydrogen peroxide, superoxide and hydroxyl ions, induce stimulation to the Permeability Transition Pore (mPTP) of the mitochondria leading to the collapse of the mitochondrial membrane potential and the release of cytochrome C. Furthermore, increased ROS activity promote nitric oxide binding to superoxide producing peroxynitrate enhancing oxidative and nitrosative stress, which results in DNA damage, chromosomal mutations, lipid peroxidation and enzyme defects [3]. Mutation of E3 ligase caused by peroxynitrate damage leads to impairment of ubiquitin-proteasome system, resulting in high levels of defective proteins, which accumulate in the Endoplasmic Reticulum (ER) promoting ER stress and ultimately cell death. Moreover, the apoptotic neuron triggers injury signals that activate microglia and promote release of cytokines such as interleukins-6 and -8. Subsequently, interleukins trigger Caspase activation along with inducible NO synthase, which further elevates formation of nitric oxide. Exposure to excessive reactive nitrite species along with enhanced production of ROS and peroxynitrate lead to dysfunction of complex-IV and complex-I activities of the mitochondria and promote mitochondrialmediated apoptosis through Caspase activation [4,5].
Affiliation:
University of Bedfordshire
Citation:
Chaudhry, Z.L, Ahmed, B.Y. (2014) 'The role of caspases in Parkinson’s Disease pathogenesis: a brief look at the mitochondrial pathway'. Austin Alzheimer's and Parkinson's Disease 1 (3) 2-5
Publisher:
Austin Publishing Group
Journal:
Austin Alzheimer's and Parkinson's Disease
Issue Date:
2014
URI:
http://hdl.handle.net/10547/565834
Additional Links:
http://austinpublishinggroup.com/aapd/download.php?file=fulltext/aapd-v1-id1017.pdf
Type:
Article
Language:
en
ISSN:
2377-357X
Appears in Collections:
Biomedical Science

Full metadata record

DC FieldValue Language
dc.contributor.authorChaudhry, Zahara Latifen
dc.contributor.authorAhmed, Bushra Y.en
dc.date.accessioned2015-08-11T10:27:31Zen
dc.date.available2015-08-11T10:27:31Zen
dc.date.issued2014en
dc.identifier.citationChaudhry, Z.L, Ahmed, B.Y. (2014) 'The role of caspases in Parkinson’s Disease pathogenesis: a brief look at the mitochondrial pathway'. Austin Alzheimer's and Parkinson's Disease 1 (3) 2-5en
dc.identifier.issn2377-357Xen
dc.identifier.urihttp://hdl.handle.net/10547/565834en
dc.description.abstractParkinson’s disease (PD) is a neurodegenerative disorder characterised by tremor, rigidity, Bradykinesia and reduced facial expression. Development of PD is considered to be the result of deficiency of the neurotransmitter dopamine, which is due to death of Dopamine-Containing Neurons (DCNs) that produce dopamine in the pars compacta region of the substantia nigra. Although the concentrated efforts of the scientific community over the last decades, the etiology of the death of DCN is yet to be understood. Oxidative stress has been considered as one of the causes of defects in the mitochondria leading to the dopaminergic cell damage [1]. Levodopa therapy is a well-known treatment for the symptoms of PD, however long term use of L-dopa causes side effects including further enhancement of oxidative stress [2]. The elevated levels of Reactive Oxidative Species (ROS) such as hydrogen peroxide, superoxide and hydroxyl ions, induce stimulation to the Permeability Transition Pore (mPTP) of the mitochondria leading to the collapse of the mitochondrial membrane potential and the release of cytochrome C. Furthermore, increased ROS activity promote nitric oxide binding to superoxide producing peroxynitrate enhancing oxidative and nitrosative stress, which results in DNA damage, chromosomal mutations, lipid peroxidation and enzyme defects [3]. Mutation of E3 ligase caused by peroxynitrate damage leads to impairment of ubiquitin-proteasome system, resulting in high levels of defective proteins, which accumulate in the Endoplasmic Reticulum (ER) promoting ER stress and ultimately cell death. Moreover, the apoptotic neuron triggers injury signals that activate microglia and promote release of cytokines such as interleukins-6 and -8. Subsequently, interleukins trigger Caspase activation along with inducible NO synthase, which further elevates formation of nitric oxide. Exposure to excessive reactive nitrite species along with enhanced production of ROS and peroxynitrate lead to dysfunction of complex-IV and complex-I activities of the mitochondria and promote mitochondrialmediated apoptosis through Caspase activation [4,5].en
dc.language.isoenen
dc.publisherAustin Publishing Groupen
dc.relation.urlhttp://austinpublishinggroup.com/aapd/download.php?file=fulltext/aapd-v1-id1017.pdfen
dc.subjectParkinson's diseaseen
dc.subjectmitochondriaen
dc.subjectmitochondrial pathwayen
dc.subjectcaspaseen
dc.subjectCascade mitochondriaen
dc.subjectoxidative stressen
dc.subjectcytochrome Cen
dc.titleThe role of caspases in Parkinson’s Disease pathogenesis: a brief look at the mitochondrial pathwayen
dc.typeArticleen
dc.contributor.departmentUniversity of Bedfordshireen
dc.identifier.journalAustin Alzheimer's and Parkinson's Diseaseen
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