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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
neuroscience
A synopsis on the role of tyrosine hydroxylase in Parkinson's disease
CNS and Neurological Disorders - Drug Targets, Volume 11, No. 4, Year 2012
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Description
Parkinson's disease (PD) is a common chronic progressive neurodegenerative disorder in elderly people. A consistent neurochemical abnormality in PD is degeneration of dopaminergic neurons in substantia nigra pars compacta, leading to a reduction of striatal dopamine (DA) levels. As tyrosine hydroxylase (TH) catalyses the formation of Ldihydroxyphenylalanine (L-DOPA), the rate-limiting step in the biosynthesis of DA, the disease can be considered as a TH-deficiency syndrome of the striatum. Problems related to PD usually build up when vesicular storage of DA is altered by the presence of either α-synuclein protofibrils or oxidative stress. Phosphorylation of three physiologically-regulated specific sites of N-terminal domain of TH is vital in regulating its kinetic and protein interaction. The concept of physiological significance of TH isoforms is another interesting aspect to be explored further for a comprehensive understanding of its role in PD. Thus, a logical and efficient strategy for PD treatment is based on correcting or bypassing the enzyme deficiency by the treatment with L-DOPA, DA agonists, inhibitors of DA metabolism or brain grafts with cells expressing a high level of TH. Neurotrophic factors are also attracting the attention of neuroscientists because they provide the essential neuroprotective and neurorestorative properties to the nigrostriatal DA system. PPAR-γ, a key regulator of immune responses, is likewise a promising target for the treatment of PD, which can be achieved by the use of agonists with the potential to impact the expression of pro- and anti-inflammatory cytokines at the transcriptional level in immune cells via expression of TH. Herein, we review the primary biochemical and pathological features of PD, and describe both classical and developing approaches aimed to ameliorate disease symptoms and its progression. © 2012 Bentham Science Publishers.
Authors & Co-Authors
Tabrez, S.
Saudi Arabia, Jeddah
King Abdulaziz University
Jabir, Nasimudeen Rehumathbeevi
Saudi Arabia, Jeddah
King Abdulaziz University
Shakil, Shazi
Saudi Arabia, Jeddah
King Abdulaziz University
Greig, Nigel H.
United States, Bethesda
National Institute on Aging Nia
Alam, Qamre
Saudi Arabia, Jeddah
King Abdulaziz University
Abuzenadah, Adel Mohammad
Saudi Arabia, Jeddah
King Abdulaziz University
Damanhouri, Ghazi Abdullah
Saudi Arabia, Jeddah
King Abdulaziz University
Kamal, Mohammad Amjad
Saudi Arabia, Jeddah
King Abdulaziz University
Statistics
Citations: 118
Authors: 8
Affiliations: 2
Identifiers
Doi:
10.2174/187152712800792785
ISSN:
18715273
e-ISSN:
19963181