Tyrosine hydroxylase as a sentinel for central and peripheral tissue responses in Parkinson's progression: Evidence from clinical studies and neurotoxin models

M. E. Johnson, Michael Francis Salvatore, S. A. Maiolo, L. Bobrovskaya

Research output: Contribution to journalReview articleResearchpeer-review

5 Citations (Scopus)

Abstract

Parkinson's disease (PD) is a common neurodegenerative disease worldwide. While the typical motor symptoms of PD are well known, the lesser known non-motor symptoms can also greatly impact the patient's quality of life. These symptoms often appear before motor impairment, therefore identifying biomarkers that may predict PD risk or pathology has been a major and challenging endeavour. Given that the loss of dopamine, and its rate-limiting enzyme tyrosine hydroxylase (TH) occurs in PD, the expression and accompanying post-translational changes in TH during PD progression could yield insight into the disruption of cellular signalling occurring in the CNS, and also in peripheral tissues wherein catecholamine function plays a role. Furthermore, changes in expression and phosphorylation of TH in the brain and periphery can potentially reveal how TH stability and function are compromised in PD. As such, these changes can reveal how catecholamine synthesis capacity is gradually compromised and how changes in cellular signalling may govern the functional status of remaining catecholaminergic neurons. This review summarises the findings of clinical PD and neurotoxin models of PD that assessed TH expression or phosphorylation in catecholaminergic pathways in the brain and relevant peripheral tissues. We propose that establishing similar changes in TH expression and function in the CNS and periphery of established neurotoxin models can be a potential reference for comparison to changes in TH in human peripheral tissues. These changes in TH expression and phosphorylation may have predictive validity to estimate risk of PD progression before motor impairment is evident.

Original languageEnglish
Pages (from-to)1-25
Number of pages25
JournalProgress in Neurobiology
Volume165-167
DOIs
StatePublished - 1 Jun 2018

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Neurotoxins
Tyrosine 3-Monooxygenase
Parkinson Disease
Phosphorylation
Catecholamines
Disease Progression
cyhalothrin
Clinical Studies
Brain
Neurodegenerative Diseases
Dopamine
Biomarkers
Quality of Life
Pathology
Neurons
Enzymes

Keywords

  • Neurotoxin models
  • Non-motor symptoms
  • Parkinson's disease
  • Tyrosine hydroxylase

Cite this

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title = "Tyrosine hydroxylase as a sentinel for central and peripheral tissue responses in Parkinson's progression: Evidence from clinical studies and neurotoxin models",
abstract = "Parkinson's disease (PD) is a common neurodegenerative disease worldwide. While the typical motor symptoms of PD are well known, the lesser known non-motor symptoms can also greatly impact the patient's quality of life. These symptoms often appear before motor impairment, therefore identifying biomarkers that may predict PD risk or pathology has been a major and challenging endeavour. Given that the loss of dopamine, and its rate-limiting enzyme tyrosine hydroxylase (TH) occurs in PD, the expression and accompanying post-translational changes in TH during PD progression could yield insight into the disruption of cellular signalling occurring in the CNS, and also in peripheral tissues wherein catecholamine function plays a role. Furthermore, changes in expression and phosphorylation of TH in the brain and periphery can potentially reveal how TH stability and function are compromised in PD. As such, these changes can reveal how catecholamine synthesis capacity is gradually compromised and how changes in cellular signalling may govern the functional status of remaining catecholaminergic neurons. This review summarises the findings of clinical PD and neurotoxin models of PD that assessed TH expression or phosphorylation in catecholaminergic pathways in the brain and relevant peripheral tissues. We propose that establishing similar changes in TH expression and function in the CNS and periphery of established neurotoxin models can be a potential reference for comparison to changes in TH in human peripheral tissues. These changes in TH expression and phosphorylation may have predictive validity to estimate risk of PD progression before motor impairment is evident.",
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Tyrosine hydroxylase as a sentinel for central and peripheral tissue responses in Parkinson's progression : Evidence from clinical studies and neurotoxin models. / Johnson, M. E.; Salvatore, Michael Francis; Maiolo, S. A.; Bobrovskaya, L.

In: Progress in Neurobiology, Vol. 165-167, 01.06.2018, p. 1-25.

Research output: Contribution to journalReview articleResearchpeer-review

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AU - Johnson, M. E.

AU - Salvatore, Michael Francis

AU - Maiolo, S. A.

AU - Bobrovskaya, L.

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