Proteomics in human Parkinson's disease research

During the last decades, considerable advances in the understanding of specific mechanisms underlying neurodegeneration in Parkinson's disease have been achieved, yet neither definite etiology nor unifying sequence of molecular events has been formally established. Current unmet needs in Parkin...

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Bibliographic Details
Published inJournal of proteomics Vol. 73; no. 1; pp. 10 - 29
Main Authors Licker, Virginie, Kövari, Enikö, Hochstrasser, Denis F., Burkhard, Pierre R.
Format Journal Article
LanguageEnglish
Published Kidlington Elsevier B.V 02.11.2009
Elsevier
Subjects
Biological and medical sciences
Biomedical Research - trends
Brain - metabolism
Brain - pathology
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Disease Progression
Diverse techniques
Fundamental and applied biological sciences. Psychology
Humans
Lewy Bodies - metabolism
Lewy Bodies - pathology
Lewy body
Medical sciences
Molecular and cellular biology
Nerve Degeneration - etiology
Nerve Degeneration - metabolism
Neurology
Parkinson Disease - cerebrospinal fluid
Parkinson Disease - etiology
Parkinson Disease - metabolism
Parkinson Disease - pathology
Parkinson's disease
Protein
Protein Processing, Post-Translational - physiology
Proteome - analysis
Proteomics
Proteomics - methods
Substantia nigra
α-synuclein
LN
VTA
Parkinson's disease
LP
Substantia nigra
ALS
CNS
UB
DUB
α-SYN
CSF
UPS
α-synuclein
AD
SNpc
2-DE
Protein
PTMs
PD
LB
LC
LCM
ROS
Proteomics
LD
TMT
MPTP
DA
HE
NM
Lewy body
Human
Alpha synuclein
Parkinson disease
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Abstract During the last decades, considerable advances in the understanding of specific mechanisms underlying neurodegeneration in Parkinson's disease have been achieved, yet neither definite etiology nor unifying sequence of molecular events has been formally established. Current unmet needs in Parkinson's disease research include exploring new hypotheses regarding disease susceptibility, occurrence and progression, identifying reliable diagnostic, prognostic and therapeutic biomarkers, and translating basic research into appropriate disease-modifying strategies. The most popular view proposes that Parkinson's disease results from the complex interplay between genetic and environmental factors and mechanisms believed to be at work include oxidative stress, mitochondrial dysfunction, excitotoxicity, iron deposition and inflammation. More recently, a plethora of data has accumulated pinpointing an abnormal processing of the neuronal protein α-synuclein as a pivotal mechanism leading to aggregation, inclusions formation and degeneration. This protein-oriented scenario logically opens the door to the application of proteomic strategies to this field of research. We here review the current literature on proteomics applied to Parkinson's disease research, with particular emphasis on pathogenesis of sporadic Parkinson's disease in humans. We propose the view that Parkinson's disease may be an acquired or genetically-determined brain proteinopathy involving an abnormal processing of several, rather than individual neuronal proteins, and discuss some pre-analytical and analytical developments in proteomics that may help in verifying this concept.
AbstractList During the last decades, considerable advances in the understanding of specific mechanisms underlying neurodegeneration in Parkinson's disease have been achieved, yet neither definite etiology nor unifying sequence of molecular events has been formally established. Current unmet needs in Parkinson's disease research include exploring new hypotheses regarding disease susceptibility, occurrence and progression, identifying reliable diagnostic, prognostic and therapeutic biomarkers, and translating basic research into appropriate disease-modifying strategies. The most popular view proposes that Parkinson's disease results from the complex interplay between genetic and environmental factors and mechanisms believed to be at work include oxidative stress, mitochondrial dysfunction, excitotoxicity, iron deposition and inflammation. More recently, a plethora of data has accumulated pinpointing an abnormal processing of the neuronal protein α-synuclein as a pivotal mechanism leading to aggregation, inclusions formation and degeneration. This protein-oriented scenario logically opens the door to the application of proteomic strategies to this field of research. We here review the current literature on proteomics applied to Parkinson's disease research, with particular emphasis on pathogenesis of sporadic Parkinson's disease in humans. We propose the view that Parkinson's disease may be an acquired or genetically-determined brain proteinopathy involving an abnormal processing of several, rather than individual neuronal proteins, and discuss some pre-analytical and analytical developments in proteomics that may help in verifying this concept.
During the last decades, considerable advances in the understanding of specific mechanisms underlying neurodegeneration in Parkinson's disease have been achieved, yet neither definite etiology nor unifying sequence of molecular events has been formally established. Current unmet needs in Parkinson's disease research include exploring new hypotheses regarding disease susceptibility, occurrence and progression, identifying reliable diagnostic, prognostic and therapeutic biomarkers, and translating basic research into appropriate disease-modifying strategies. The most popular view proposes that Parkinson's disease results from the complex interplay between genetic and environmental factors and mechanisms believed to be at work include oxidative stress, mitochondrial dysfunction, excitotoxicity, iron deposition and inflammation. More recently, a plethora of data has accumulated pinpointing an abnormal processing of the neuronal protein alpha-synuclein as a pivotal mechanism leading to aggregation, inclusions formation and degeneration. This protein-oriented scenario logically opens the door to the application of proteomic strategies to this field of research. We here review the current literature on proteomics applied to Parkinson's disease research, with particular emphasis on pathogenesis of sporadic Parkinson's disease in humans. We propose the view that Parkinson's disease may be an acquired or genetically-determined brain proteinopathy involving an abnormal processing of several, rather than individual neuronal proteins, and discuss some pre-analytical and analytical developments in proteomics that may help in verifying this concept.
Author Kövari, Enikö
Hochstrasser, Denis F.
Burkhard, Pierre R.
Licker, Virginie
Author_xml – sequence: 1
  givenname: Virginie
  surname: Licker
  fullname: Licker, Virginie
  organization: Neuroproteomics Group, University Medical Center, Faculty of Medicine, University of Geneva, Switzerland
– sequence: 2
  givenname: Enikö
  surname: Kövari
  fullname: Kövari, Enikö
  organization: Department of Psychiatry, Geneva University Hospitals, Switzerland
– sequence: 3
  givenname: Denis F.
  surname: Hochstrasser
  fullname: Hochstrasser, Denis F.
  organization: Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Switzerland
– sequence: 4
  givenname: Pierre R.
  surname: Burkhard
  fullname: Burkhard, Pierre R.
  email: Pierre.Burkhard@hcuge.ch
  organization: Neuroproteomics Group, University Medical Center, Faculty of Medicine, University of Geneva, Switzerland
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Issue 1
Keywords LN
VTA
Parkinson's disease
LP
Substantia nigra
ALS
CNS
UB
DUB
α-SYN
CSF
UPS
α-synuclein
AD
SNpc
2-DE
Protein
PTMs
PD
LB
LC
LCM
ROS
Proteomics
LD
TMT
MPTP
DA
HE
NM
Lewy body
Human
Alpha synuclein
Parkinson disease
Language English
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PublicationTitle Journal of proteomics
PublicationTitleAlternate J Proteomics
PublicationYear 2009
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Elsevier
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Snippet During the last decades, considerable advances in the understanding of specific mechanisms underlying neurodegeneration in Parkinson's disease have been...
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SubjectTerms Biological and medical sciences
Biomedical Research - trends
Brain - metabolism
Brain - pathology
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Disease Progression
Diverse techniques
Fundamental and applied biological sciences. Psychology
Humans
Lewy Bodies - metabolism
Lewy Bodies - pathology
Lewy body
Medical sciences
Molecular and cellular biology
Nerve Degeneration - etiology
Nerve Degeneration - metabolism
Neurology
Parkinson Disease - cerebrospinal fluid
Parkinson Disease - etiology
Parkinson Disease - metabolism
Parkinson Disease - pathology
Parkinson's disease
Protein
Protein Processing, Post-Translational - physiology
Proteome - analysis
Proteomics
Proteomics - methods
Substantia nigra
α-synuclein
Title Proteomics in human Parkinson's disease research
URI https://dx.doi.org/10.1016/j.jprot.2009.07.007
https://www.ncbi.nlm.nih.gov/pubmed/19632367
Volume 73
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