An update on pathogenesis and clinical scenario for Parkinson's disease: diagnosis and treatment

Abstract

In severe cases, Parkinson's disease causes uncontrolled movements known as motor symptoms such as dystonia, rigidity, bradykinesia, and tremors. Parkinson's disease also causes non-motor symptoms such as insomnia, constipation, depression and hysteria. Disruption of dopaminergic and non-dopaminergic neural networks in the substantia nigra pars compacta is a major cause of motor symptoms in Parkinson's disease. Furthermore, due to the difficulty of clinical diagnosis of Parkinson's disease, it is often misdiagnosed, highlighting the need for better methods of detection. Treatment of Parkinson's disease is also complicated due to the difficulties of medications passing across the blood-brain barrier. Moreover, the conventional methods fail to solve the aforementioned issues. As a result, new methods are needed to detect and treat Parkinson's disease. Improved diagnosis and treatment of Parkinson's disease can help avoid some of its devastating symptoms. This review explores how nanotechnology platforms, such as nanobiosensors and nanomedicine, have improved Parkinson's disease detection and treatment. Nanobiosensors integrate science and engineering principles to detect Parkinson's disease. The main advantages are their low cost, portability, and quick and precise analysis. Moreover, nanotechnology can transport medications in the form of nanoparticles across the blood-brain barrier. However, because nanobiosensors are a novel technology, their use in biological systems is limited. Nanobiosensors have the potential to disrupt cell metabolism and homeostasis, changing cellular molecular profiles and making it difficult to distinguish sensor-induced artifacts from fundamental biological phenomena. In the treatment of Parkinson's disease, nanoparticles, on the other hand, produce neurotoxicity, which is a challenge in the treatment of Parkinson's disease. Techniques must be developed to distinguish sensor-induced artifacts from fundamental biological phenomena and to reduce the neurotoxicity caused by nanoparticles.

Keywords: Biomarker; Diagnostics; Disease management; Nanobiosensor; Neurodegenerative disease; Parkinson’s disease.

Fig. 1

Aggregation of alpha-synuclein and Lewy bodies in Parkinson’s disease. Parkinson's disease is characterized by loss of dopaminergic neurons in the substantia nigra pars compacta and affects the brain, spinal cord, and nerves connecting the brain and spinal cord. The presence of Lewy bodies is a symptom of Parkinson's disease. Lewy bodies are an intracellular aggregation of alpha-synuclein in the brain. Pathological oligomers and higher-order aggregates of misfolded alpha-synuclein proteins form fibrils and aggregates in Parkinson's disease brain neurons as Lewy bodies. The presence of Lewy bodies in the brainstem impairs the production of dopamine. This leads to oxidative stress, axonal dysfunction, protein sequestration, mitochondrial dysfunction, synaptic dysfunction, and suppression of the ubiquitin–proteasome system

Fig. 2

Clinical Management of Parkinson’s disease. Dopamine is the chemical messenger responsible for smooth and purposeful movements. Dopamine agonists act in the brain in the same way as dopamine. This causes neurons in the brain to use dopamine agonists to relieve the symptoms of Parkinson's disease movement disorder. When an MAO-B inhibitor is taken at the same time, the breakdown of levodopa and dopamine in the brain is slowed. This improves the effect of levodopa. Catechol-O-methyltransferase (COMT) is a neurotransmitter-degrading enzyme that breaks down dopamine and other neurotransmitters. The breakdown of levodopa and dopamine is reduced when levodopa medications are combined with a COMT inhibitor. This enhances the effect of levodopa by increasing its availability in the brain

Fig. 3

Motor and non-motor symptoms of Parkinson's disease. Parkinson's disease is characterized by various motor and non-motor symptoms. Tremor, rigidity, freezing, bradykinesia, dystonia, and other motor abnormalities are common in patients with Parkinson’s disease. Despite its status as a paradigmatic movement disorder, Parkinson's disease is accompanied by a wide range of non-motor symptoms in addition to motor symptoms. As the disease progresses, non-motor symptoms become more common. The common symptoms are depression, hyposmia, sleep disturbances, fatigue, and constipation, may manifest before motor symptoms. The specific clinicopathologic correlates for most of these nonmotor features are still unclear

Fig. 4

Dopamine neuron function. Dopamine is a neurotransmitter in the brain, a chemical released by neurons to transmit messages to other neurons. There are several different dopamine pathways in the brain, one of which is critical for the motivational component of reward-motivated behavior

Fig. 5

Treatment for Parkinson’s disease using nanotechnology. Nanoparticles can be synthesized and manipulated to obtain various properties. Due to their physicochemical properties, engineered nanomaterials have a number of characteristics, including the ability to cross the blood–brain barrier. Nanomedicine can significantly improve the treatment of Parkinson's disease. Nanomedicines can improve half-life, bioavailability, and therapeutic benefit. In addition, nanomedicines can help alleviate L- DOPA-induced dyskinesia

Fig. 6

Nanobiosensor. Signal transduction is used to fuel biosensors, with the transducer detecting the interaction and generating a signal. The primary concept of how a nanobiosensor works is to bind bioanalytes of interest to bioreceptors, which then drive the physicochemical signal associated with the binding. The chemical signal is converted to an electrical signal via electrodes in nanobiosensors. Nanobiosensors could also detect analytes such as CSF, antibodies, and other molecules of interest

Fig. 7

Detection of Parkinson’s disease using nanobiosensor. Biosensors are devices that provide a solid surface for probe-target interaction and then convert that interaction into a measurable signal. Optical, cantilever deflections, electrical, and electrochemical signals are examples of signal output. For example, nanobiosensors could be used as electrochemical sensors to detect Parkinson's disease based on alpha-synuclein aggregation after partitioning into different concentrations