Title:Targeting Parkinson’s - Tyrosine Hydroxylase and Oxidative Stress as Points of Interventions
VOLUME: 11 ISSUE: 4
Author(s):Mohd Shahnawaz Khan, Shams Tabrez, Medha Priyadarshini, Shubha Priyamvada and Mohd M. Khan
Affiliation:Department of Biochemistry, King Saud University, Riyadh, Saudi Arabia.
Keywords:Oxidative stress, Parkinson’s disease, phytochemicals, tyrosine hydroxylase.
Abstract:Parkinson's disease (PD) is characterized by the progressive loss of the dopaminergic neurons leading to
decrease in striatal dopamine (DA) levels. In the present review, our focus was on recent advances in the treatment
procedures of PD to achieve an increase in deficient tyrosine hydroxylase (TH) activity and/or expression. Stimulation of
residual TH activity by the cofactors, 6R-L-erythro-tetrahydrobiopterin (BPH4) or NADH, or by brain transplant of
natural TH-containing cells (fetal substantia nigra) or genetically engineered TH-containing cells, has been tried
experimentally and clinically lately. As a promising approach to the gene therapy, intrastriatal expression of DAsynthesizing
enzymes through transduction with separate adeno-associated virus (AAV) vectors/ marrow stromal cells
(MSCs) or nonviral intravenous administration of rat transferrin receptor monoclonal antibody (TfRmAb)-targeted
PEGylated immunoliposomes (PILs) has been found to be effective in animal models. Oxidative stress has been identified
as one of the intermediary risk factors that could initiate and/or promote degeneration of DA neurons. TH itself is a prime
target of oxidative/nitrosative injury. Certain superoxide dismutase and catalase mimetic prevented nitration of TH in
cultured dopaminergic neurons. Therefore, development of therapeutic agents that can prevent formation of or specifically
remove nitrating agents without interfering with normal neuronal function may protect protein from inactivation
and provide means of limiting neuronal injury in PD. Non-pharmacological approaches such as diet therapy or use of
active constituents of plants and phytomedicines have also emerged as a new - area of high interest. New treatment
strategies for TH dysfunction rectification, a provision for neuroprotection in PD, seem to be on the horizon with many
therapies under investigation.
