Serum uric acid is a promptly affirmed neuroprotective agent. Its concentration levels in Parkinson’s disease (PD) were found to be an efficient diagnostic biomolecule. Although it is able to minimize PD associated disability and symptoms worsening by preventing the formation of reactive oxygen species, Lewy bodies, abnormal proteins and intracellular stress. Bowel bladder, swallowing, speech, memory and sleep disorders are some of the non-motor symptoms of Parkinson’s disease. Its motor symptoms include tremors, muscular rigidity, cramps, gait and body balance disturbances. Geriatric studies consider Parkinson as second most worldwide prevailing disorder associated with body shaking syndrome accompanied by dopamine deficits, generation and accumulation of brain damaging proteins, ROS and other metabolites. Uric acid is a devouerer of free oxygen, hydroxyl radicals and superoxide dimutase additionally it chelates the Ferric molecules to diminish its negative effects in PD brain. Measurement of serum uric acid is a potent biomarker for several brain degenerating diseases, particularly Parkinsonism, whilst its increased serum extent regulates the brain protective mechanism especially by reducing harmful oxidation.
ABSTRACT
Serum uric acid a promptly affirmed neuroprotective agent. Its concentration levels in Parkinson’s disease found to be an efficient diagnostic biomolecule. Although it is able to minimize PD associated disability and symptoms worsening by preventing the formation of reactive oxygen species, Lewy bodies, abnormal proteins and intracellular stress. Bowel bladder, swallowing, speech, memory and sleep disorders are some of the non-motor symptoms of Parkinson’s disease. Its motor symptoms include tremors, muscular rigidity, cramps, gait and body balance disturbances. Geriatric studies consider Parkinson as second most worldwide prevailing disorder associated with body shaking syndrome accompanied by dopamine deficits, generation and accumulation of brain damaging proteins, ROS and other metabolites. Uric acid is a devourer of free oxygen, hydroxyl radicals and superoxide dimutase additionally it chelates the Ferric molecules to diminish its negative effects in PD brain. Measurement of serum uric acid is a potent biomarker for several brain degenerating diseases particularly Parkinsonism whilst its increased serum extent regulates the brain protective mechanism especially by reducing harmful oxidation.
Keywords: serum uric acid (SUA), Parkinson’s disease, reactive oxygen species, Dopamine and oxidative stress.
INTRODUCTION
Serum uric acid is a copiously found natural antioxidant biochemical moiety in human plasma (1). Structurally it is hetero cyclic but more commonly in human blood and urine it appears as urate salts. Excessive protein and disaccharides or purine rich diet are its main sources whereas people on vegan diet showed less serum uric acid levels (2).
In humans Several disorders are linked to aberrant uric acid values. Hence, analysis of serum uric acid concentration can be a valuable diagnostic tool as well as a good cure (3). SUA upraise in cardiac disease, gout, hypertension, stroke and decreases in certain brain disorders such as multiple sclerosis and Parkinsonism (4). Declined SUA observed in genetic PD and in such inherited cases it can act as an efficient diagnostic biomarker (5). Up till 2016 Parkinson disease affected more than 6 million people globally (6). Male population above 70 years of age are most prominently affected by this brain disease (7). Parkinson's is an old age, second most frequently prevailing brain disease and as the elder community is increasing across the world its treatment cost burdens are also expanding. To overcome this drastic situation there is an eager need to develop and discover the PD diagnostic biomarker (8). According to international Parkinson and movement disorder society PD includes cluster of autonomic, neuropsychiatric, motor and non-motor dysfunctions (9). Other common distinctive features include tremors at rest and unstable posture (10).pathophysiological reason for these PD related symptoms is improper working of basal ganglia followed by Dopamine deficit(11). Bradykinesia, tremors and rigidity in Parkinson’s is due to degradation of dopaminergic neurons of substantia nigra (12).
PRODUCTION OF ROS AND OXIDATIVE STRESS DEVELOPMENT IN PD
Dopamine metabolism generates the reactive oxygen species which shows the redox activity of cells resulting in an increased oxidative stress. Aggregation of ROS leads to oxidative destruction of nucleic acids, lipids and destructive protein production. In early PD stages oxidative stress is a firm feature that appears before the neurons dies (13). ROS are end-products of aerobic respiration. Among the total quantity of oxygen consumed by a human body only 5% produces the active oxygen metabolites and over formation of ROS is referred as oxidation stress (14).
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Fig-1 Biomolecules in Parkinson's disease
CLASSICAL DRUGS IN PD TREATMENT AND THEIR LIMITATIONS
Levodopa is regarded as a first line treatment for Parkinson’s, but it has limitations, for example a major adverse effect of Levodopa use is dyskinesia, which are irregular, haphazard, constant meaningless movements (15). In large number of Parkinson’s affected cases it has been observed that the Dopamine augmenting drugs contribute to alcoholism, drug abuse and several other psychological problems (16). In penultimate stage dopamine neuronal cells of substantia nigra underwent apoptosis leading to cessation of dopamine synthesis followed by atrophy and wrecking of brain tissue. Levodopa is a classic drug to overcome the effects of theses perilous brain alterations, but now anti-inflammatory substances are proclaimed to be a much better option (17).
URIC ACID DECREASES OXIDATIVE STRESS IN PD
Uric acid is considered as to be the very first anti-inflammatory antioxidant biomolecule capable of declining the chances of PD development up to 33% male subjects and can minimize its progression. The neuroprotectant pursuit of SUA is achieved by its scavenging ability to decrease hoarding of oxygen radicals, also by occluding iron based oxidation activities furthermore by improving calcium concentration via mitochondrial functions conservation (18). Iron is a typical product of usual metabolic activities of a cell but in PD it is a reason of protein misfolding and their aggregation (19).iron acts as a catalyzer of oxidative stress process and to hinder this process SUA chelates the iron molecules. Besides chelation, SUA also reduces oxidative stress by scavenging peroxides, super oxides and free radicals. Superoxides are formed during conversion of hypoxanthine into uric acid (20).
Neurogenesis is the tendency of brain to generate new neurons and reinforce their synapses thorough out life. Defective neurogenesis is an alarming complication of Parkinsonism. SUA level increasing therapeutic strategies can ameliorate neurogenesis by modifying mitochondrial functionality (21).
Inability to speak or difficulty in correct pronunciation, memory deficits, inadequate planning skills and inability to interpret face expressions are the significant cognitive impairments found in Parkinson patients(22).
SUA IN DIAGNOSIS AND IMPROVEMENT OF PD
Low SUA levels are highly linked with Cognitive impairments like forgetfulness in brain disorders including Alzheimer and Parkinson are due improper neuronal synapses (23). In Parkinson's Production of Lewy bodies are also a major reason of cognitive defects and decline (24). Lewy body dementia is characterized by decreased attentiveness, suppressed mental arousal and orthostatic hypotension (25). Lewy body in PD is composed of a misfolded alpha-synuclein protein filaments, mitochondria, lipids, Ubiquitin protein etc. (26). A drastic consequence of increased oxidative stress is accumulation of alpha-synuclein that is responsible for mitochondrial dysfunction and neuronal death (27). SUA degenerates and lowers the Lewy bodies accumulation by instigating the process of autophagy (28). Autophagy is a defensive, intracellular deteriorating, reprocessing mechanism necessary for homeostasis (29). Elevated SUA performs the process of autophagy and has a protective role (30).
CONCLUSION
Purine disintegration generates the uric acid. Besides its toxicity, its elevated proportions in serum can serve as a hunter for brain degenerating ions, metabolites and chemical bodies more significantly in Parkinson’s disease. Parkinson’s is a painful disability causing disease. It can be prevented, or its severity can be minimized by decreasing neuron damage via maintaining normal SUA level.
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