Introduction: Parkinson's disease (PD) is a progressive and severe neurological disorder of the central nervous system. The main risk factors are age and environmental factors. This disease is more common in the elderly (over 60 years old). The reports of James Parkinson, an Italian surgeon, led to the identification of Parkinson's disease. The most obvious feature of this disease is the reduction of cells in several concentrated areas of the substantia nigra and the accumulation of alpha-synuclein protein and its increased concentration, especially in the brain stem, spinal cord, and cerebral cortex areas. This disease is caused by an imbalance between the basal ganglia as a result of dopamine inhibition of the putamen nucleus, which increases the inhibition of the thalamus, decreases the excitatory output of the thalamus, and causes movement disorders.
Symptoms: Parkinson's disease is caused by less production of dopamine, a brain neurotransmitter in the neurons of the substantia nigra of the brain. Dopamine as a brain neurotransmitter is very important in another area of the brain called ganglia. This area of the brain is responsible for organizing the brain's commands for movement. Norepinephrine is reduced in people with Parkinson's disease. This chemical is effective in the functioning of the sympathetic nervous system. Its deficiency is associated with non-motor symptoms of Parkinson's.
The movement symptoms of Parkinson's include: muscle stiffness, resting tremor, akinesia, bradykinesia, weakness in maintaining balance and reduction of unconscious and natural body movements. Non-motor symptoms of Parkinson's include: depression and anxiety, memory impairment, hallucinations and delusions, swallowing and chewing disorders, urinary problems and sleep disorders.
Effect of lipids in disease: Lipids are biomolecules that are soluble in organic and non-polar solvents and are considered as components of biological membranes. Different groups of fat can play a role in Parkinson's disease. Research shows that changing the structure of fatty acids and replacing long-chain unsaturated acids with saturated fatty acids, phosphatidylcholine, phosphatidyl-inositol, phosphatidyl-serine, cholesterol, ganglioside, cerebroside, and sphingolipids are effective in PD.
Alpha-synuclein (AS) is a small protein that is abundantly expressed in the brain, but is mainly located in the synaptic terminal. After binding to the membrane, this protein is effective in synaptic plasticity. Normally, after AS protein binds to the membrane, the initial 95 residues of this protein undergo a conformational transition. In this case, it turns from a random coil to a helix. Changes in the nature and chemical properties of lipids lead to the tendency of AS protein to aggregate, leading to cytotoxicity. Recent studies suggest that this synucleopathy may be a protein-induced lipidopathy. Indeed, an imbalance in cellular lipid homeostasis creates a process that leads to fibrillar aggregation of AS protein. In fact, lipidopathy and proteinopathy simultaneously cause the symptoms of this disease.
Methods: Animal studies on Parkinson's disease have shown that lipid damage is effective in the occurrence of the disease. Animal models showed that changes in lipids affect dopaminergic neurons and glial cells. This effect is especially on microglia and astrocytes and is associated with accumulation of alpha-synuclein protein in dopaminergic neurons. which itself causes vulnerability in the disease process. Triglyceride lipid levels are also associated with an inflammatory marker in the brain. Examining animal models showed that changes in a specific cell in the brain can lead to Parkinson's disease.
Results: Classically, PD was thought to be a lipid-mediated proteinopathy. In this hypothesis, the incorrect folding of this protein in the form of B-Sheet leads to the accumulation of this protein in Lewy bodies and causes an imbalance in protein folding and destruction, and ultimately leads to neurological disorder and death due to the oligomerization of this protein. But new investigations in Lewy bodies and animal models showed that this synucleopathy may be protein-induced lipidopathy.
Conclusion: Changes in the content of lipids have far-reaching consequences in the field of normal nerve and brain function. The composition of lipid content is not only related to the genes involved in lipid metabolism, but endogenous factors such as food fats, lifestyle, sleep patterns, drug effects and food selection are also effective in it. To validate these studies, the relationship between lipids and Parkinson's disease is needed to help identify biomarkers and develop drug targets and treatments.
Keywords: Parkinson's disease, dopamine, norepinephrine, lipids, alpha-synuclein protein