Neurotransmitter that is deficient in patients with parkinson disease

Highlights

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Neurotransmitter receptors are potent target in neurodegenerative diseases.

Neurotransmitter levels and receptors are altered in Parkinson's Disease (PD).

Restoration of different neurotransmitter levels alleviates symptoms of PD.

Neuroprotective effects are promoted by neurotransmitter receptors.

Activation/inhibition of neurotransmitter receptors show anti-dyskinetic effects.

Abstract

Neurotransmitters are considered as a fundamental regulator in the process of neuronal growth, differentiation and survival. Parkinson's Disease (PD) occurs due to extensive damage of dopamine-producing neurons; this causes dopamine deficits in the midbrain, followed by the alternation of various other neurotransmitters (glutamate, GABA, serotonin, etc.). It has been observed that fluctuation of neurotransmission in the basal ganglia exhibits a great impact on the pathophysiology of PD. Dopamine replacement therapy, such as the use of L-DOPA, can increase the dopamine level, but it majorly ameliorates the motor symptoms and is also associated with long-term complications (for e.g., LID). While the non-dopaminergic system can efficiently target non-motor symptoms, for instance, the noradrenergic system regulates the synthesis of BDNF via the MAPK pathway, which is important in learning and memory. Herein, we briefly discuss the role of different neurotransmitters, implementation of neurotransmitter receptors in PD. We also illustrate the recent advances of neurotransmitter-based drugs, which are currently under in vivo and clinical studies. Reinstating normal neurotransmitter levels has been believed to be advantageous in the treatment of PD. Thus, there is an increasing demand for drugs that can specifically target the neurotransmission system and reinstate the normal levels of neurotransmitters, which might prevent or delay neurodegeneration in PD.

Graphical abstract

Neurotransmission alternations perform a vital role in developing Parkinson's Disease (PD), which is regulated by several neurotransmitters. In the midbrain region, the extensive damage of dopamine-producing neurons causes PD and aggregation of α-synuclein protein represents the hallmark of PD pathogenesis. This dopamine deficiency cause changes in the basal ganglia circuit and also alters levels of numerous neurotransmitters apart from dopamine, including Glutamate (GLU), GABA, Noradrenaline (NA), Acetylcholine (ACh), Histamine (HA), and Serotonin (5-HT), but their role in PD is not yet fully explored. Dopamine replacement therapy is employed to restore dopamine levels and alleviate PD symptoms. Levodopa (L-DOPA) is a precursor of dopamine, and it is considered as the golden therapy for PD patients as it can rescue motor impairment and improve quality of life, but long-term administration of L-DOPA is linked with severe complications like Levodopa-induced dyskinesia (LID). By restoring the levels of different neurotransmitters, PD symptoms might be controlled and can also show anti-dyskinetic effects. Various in silico studies to perform virtual screening, target selection from several neurotransmitter receptors etc., are going on, followed by the in vitro assays; commonly used cell lines in PD are HEK293 and SH-SY5Y Cells. In vivo studies are widely done in 6-OHDA rodent/murine models and MPTP primate models. To date, very few drugs are available to treat PD symptoms, and no medication is known to cure PD. Neurotransmitters receptors might serve as a potential target against PD, and extensive research is required in this area in the near future.

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Keywords

Neurotransmitter

Neurotransmission

Parkinson's disease

Neurodegeneration

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