Role of dopamine in the pathophysiology of Parkinson’s disease

Translational Neurodegeneration, Journal Year: 2023, Volume and Issue: 12(1)

Published: Sept. 18, 2023

A pathological feature of Parkinson's disease (PD) is the progressive loss dopaminergic neurons and decreased dopamine (DA) content in substantia nigra pars compacta PD brains. DA neurotransmitter neurons. Accumulating evidence suggests that interacts with environmental genetic factors to contribute pathophysiology. Disturbances synthesis, storage, transportation metabolism have been shown promote neurodegeneration various models. unstable can undergo oxidation produce multiple reactive toxic by-products, including oxygen species, quinones, 3,4-dihydroxyphenylacetaldehyde. Here we summarize highlight recent discoveries on DA-linked pathophysiologic pathways, discuss potential protective therapeutic strategies mitigate complications associated DA.

Language: Английский

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Distinct neurochemical influences on fMRI response polarity in the striatum

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 1, 2024

Abstract The striatum, known as the input nucleus of basal ganglia, is extensively studied for its diverse behavioral roles. However, relationship between neuronal and vascular activity, vital interpreting functional magnetic resonance imaging (fMRI) signals, has not received comprehensive examination within striatum. Here, we demonstrate that optogenetic stimulation dorsal striatal neurons or their afferents from various cortical subcortical regions induces negative fMRI responses in rats, manifesting vasoconstriction. These occur even with heightened confirmed by electrophysiology fiber-photometry. In parallel, midbrain dopaminergic neuron modulation, coupled electrochemical measurements, establishes a link vasodilation dopamine release. Intriguingly, vivo intra-striatal pharmacological manipulations during highlight critical role opioidergic signaling generating This observation substantiated detecting vasoconstriction brain slices after synthetic opioid application. humans, aimed at increasing activity likewise elicit responses. Our results emphasize necessity considering vasoactive neurotransmission alongside when signal.

Language: Английский

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Epigallocatechin-3-gallate: A phytochemical as a promising drug candidate for the treatment of Parkinson’s disease

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 12, 2022

Epigallocatechin 3-gallate (EGCG), an abundant polyphenolic component derived from green tea extract, possesses versatile bioactivities that can combat many diseases. During the last decade, EGCG was shown to be effective in experimental models of Parkinson's disease (PD). Several studies have suggested it has pleiotropic neuroprotective effects, which enhanced appeal as a therapeutic strategy PD. In this review, we compiled recent updates and knowledge molecular mechanisms underlying effects We focused on apoptosis, oxidative stress, inflammation, ferroptosis, modulation dopamine production, aggregation α-synuclein. The review highlights pharmacological features its implications Taken together, accumulated data indicate is promising compound for treatment

Language: Английский

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Neuroprotection and Disease Modification by Astrocytes and Microglia in Parkinson Disease

Antioxidants, Journal Year: 2022, Volume and Issue: 11(1), P. 170 - 170

Published: Jan. 17, 2022

Oxidative stress and neuroinflammation are common bases for disease onset progression in many neurodegenerative diseases. In Parkinson disease, which is characterized by the degeneration of dopaminergic neurons resulting dopamine depletion, pathogenesis differs between hereditary solitary forms often unclear. addition to pathogenicity alpha-synuclein as a pathological marker, involvement itself its interactions with glial cells (astrocyte or microglia) have attracted attention. Pacemaking activity, hallmark neurons, essential homeostatic maintenance adequate concentrations synaptic cleft, but it imposes burden on mitochondrial oxidative glucose metabolism, leading reactive oxygen species production. Astrocytes provide endogenous neuroprotection brain producing releasing antioxidants response stress. Additionally, protective function astrocytes can be modified microglia. Some types microglia themselves thought exacerbate pro-inflammatory factors (M1 microglia). Although these inflammatory may further trigger conversion astrocytes, induce astrocytic neuroprotective effects (A2 astrocytes) simultaneously. Interestingly, both express receptors, upregulated presence neuroinflammation. The anti-inflammatory receptor stimulation also attracting attention because functions greatly affected depletion therapeutic replacement disease. this review article, we will focus antioxidative their synergism dopamine.

Language: Английский

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Current Treatments and New, Tentative Therapies for Parkinson’s Disease

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(3), P. 770 - 770

Published: Feb. 25, 2023

Parkinson’s disease (PD) is a neurodegenerative pathology, the origin of which associated with death neuronal cells involved in production dopamine. The prevalence PD has increased exponentially. aim this review was to describe novel treatments for that are currently under investigation and study possible therapeutic targets. pathophysiology based on formation alpha-synuclein folds generate Lewy bodies, cytotoxic reduce dopamine levels. Most pharmacological target symptoms. These include aimed at reducing accumulation (epigallocatechin), its clearance via immunotherapy, inhibiting LRRK2, upregulating cerebrosidase (ambroxol). continues be pathology unknown generates significant social cost patients who suffer from it. Although there still no definitive cure present, numerous available symptomatology addition other alternatives investigation. However, approach should combination non-pharmacological strategies maximise outcomes improve symptomatological control these patients. It therefore necessary delve deeper into order quality life

Language: Английский

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Brain‐derived extracellular vesicles: Potential diagnostic biomarkers for central nervous system diseases

Psychiatry and Clinical Neurosciences, Journal Year: 2023, Volume and Issue: 78(2), P. 83 - 96

Published: Oct. 25, 2023

Extracellular vesicles (EVs) are membrane‐enclosed nanovesicles secreted by cells into the extracellular space and contain functional biomolecules, e.g. signaling receptors, bioactive lipids, nucleic acids, proteins, which can serve as biomarkers. Neurons glial secrete EVs, contributing to various physiological pathological aspects of brain diseases. EVs confer their role in bidirectional crosstalk between central nervous system (CNS) periphery owing distinctive ability cross unique blood–brain barrier (BBB). Thus, blood, cerebrospinal fluid (CSF), urine be intriguing biomarkers, enabling minimally invasive diagnosis CNS Although there has been an enormous interest evaluating promising lack ultra‐sensitive approaches for isolating detecting brain‐derived (BDEVs) hindered development efficient This review presents recent salient findings exosomal focusing on disorders. We summarize highly sensitive sensors EV detection state‐of‐the‐art methods single detection. Finally, prospect developing advanced analysis non‐invasive diseases is presented.

Language: Английский

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Research progress on the kynurenine pathway in the prevention and treatment of Parkinson’s disease

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 38(1)

Published: June 29, 2023

Parkinson's disease (PD) is characterised by progressive death of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) and pathological accumulation α-synuclein fibrils, as well central nervous system inflammation. Elevated levels inflammatory factors PD disrupt kynurenine pathway (KP) favour activation excitotoxic branches, leading to a significant reduction neuroprotective metabolite kynurenic acid (KYNA) increase neurotoxic quinolinic (QUIN), which exacerbates excitotoxicity amplifies response, closely related occurrence development PD. KYNA analogs, precursor drugs, KP enzyme modulators may represent new therapeutic strategy for This article reviews role neurodegenerative pathology its prevention treatment, aiming provide necessary theoretical basis ideas study neurobiological mechanisms underlying PD-related behavioural dysfunction targeted interventions.

Language: Английский

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The Impact of Neurotransmitters on the Neurobiology of Neurodegenerative Diseases

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15340 - 15340

Published: Oct. 19, 2023

Neurodegenerative diseases affect millions of people worldwide. result from progressive damage to nerve cells in the brain or peripheral nervous system connections that are essential for cognition, coordination, strength, sensation, and mobility. Dysfunction these functions is associated with Alzheimer's disease, Parkinson's Huntington's Amyotrophic lateral sclerosis, motor neuron disease. In addition these, 50% living HIV develop a spectrum cognitive, motor, and/or mood problems collectively referred as HIV-Associated Neurocognitive Disorders (HAND) despite widespread use combination antiretroviral therapies. Neuroinflammation neurotransmitter systems have pathological correlation play critical role developing neurodegenerative diseases. Each has unique pattern dysregulation system, which been attributed different forms cell-specific neuronal loss. this review, we will focus on discussion regulation dopaminergic cholinergic systems, more commonly disturbed disorders. Additionally, provide evidence hypothesis disturbances neurotransmission contribute loss observed Further, highlight dopamine mediator injury context NeuroHIV. This review need further investigate their etiology

Language: Английский

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Overview of Movement Disorders Secondary to Drugs

Clinics and Practice, Journal Year: 2023, Volume and Issue: 13(4), P. 959 - 976

Published: Aug. 18, 2023

Drug-induced movement disorders affect a significant percentage of individuals, and they are commonly overlooked underdiagnosed in clinical practice. Many comorbidities can these making the diagnosis even more challenging. Several variables, including genetics, environmental factors, aging, play role pathophysiology conditions. The Diagnostic Statistical Manual Mental Disorders (DSM) International Classification Diseases Related Health Problems (ICD) most used classification systems categorizing drug-induced disorders. This literature review aims to describe abnormal movements associated with some medications illicit drugs. Myoclonus is probably poorly described disorder, which reports do not electrodiagnostic studies. Therefore, information available insufficient for neuroanatomical source myoclonus. parkinsonism rarely adequately evaluated but should be assessed radiotracers when techniques available. Tardive dyskinesias encompass various movements, chorea, athetosis, ballism. Some authors include temporal relationship define tardive syndromes other disorders, such as dystonia, tremor, ataxia. Antiseizure antipsychotics among thoroughly drug classes

Language: Английский

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The High-Precision Liquid Chromatography with Electrochemical Detection (HPLC-ECD) for Monoamines Neurotransmitters and Their Metabolites: A Review

Molecules, Journal Year: 2024, Volume and Issue: 29(2), P. 496 - 496

Published: Jan. 19, 2024

This review highlights the advantages of high-precision liquid chromatography with an electrochemical detector (HPLC-ECD) in detecting and quantifying biological samples obtained through intracerebral microdialysis, specifically serotonergic dopaminergic systems: Serotonin (5-HT), 5-hydroxyindolacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic (DOPAC), dopamine (DA), 3-metoxytryptamin (3-MT) homovanillic (HVA). Recognized for its speed selectivity, HPLC enables direct analysis microdialysis without complex derivatization. Various chromatographic methods, including reverse phase (RP), are explored neurotransmitters (NTs) metabolites separation. Electrochemical (ECD), particularly glassy carbon (GC) electrodes, is emphasized simplicity sensitivity, aimed at enhancing reproducibility optimization strategies such as modified electrode materials. paper underscores determination limits detection (LOD) quantification (LOQ) linear range (L.R.) showcasing potential real-time monitoring compounds concentrations. A non-exhaustive compilation literature values LOD, LOQ, L.R. from recent publications included.

Language: Английский

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