Displaying publications 1 - 20 of 27 in total

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  1. Fulltext The potential role of herbal products in the treatment of Parkinson's disease
    Amro MS, Teoh SL, Norzana AG, Srijit D
    Clin Ter, 2018 2 16;169(1):e23-e33.
    PMID: 29446788 DOI: 10.7417/T.2018.2050
    Parkinson's disease (PD) is a multifactorial disorder of the nervous system in which there is a progressive loss of dopaminergic neurons. There is a disturbance in the movement in PD and these include resting tremors, rigidity, bradykinesia or akinesia, disturbance, posture and freezing (motor block). The substantia nigra and other parts of the brain are commonly affected. The disorder could be related to oxidative stress and there is an important role of reactive oxygen species (ROS). A number of herbal products contain active components which are known to possess antioxidant action. Hence, the potential role of herbal products in treating PD cannot be undermined. In the present narrative review, the main aim is to discuss the pathogenesis of PD, define the role of different potential herbal extracts on its pathogenesis which may form the basis of treatment. We also discuss in detail the active chemical compounds present each herb which are effective in the treatment of PD. These herbs include Baicalei, Erythrina velutin, Resveratrol, Peganum Harmal, Curcuma longa (Zingiberaceae), Carthamus tinctorius L. (Safflower), Pueraria lobate, Juglandis Semen (Walnut), Tianma Gouteng Yin (TGY), Lycium barbarum L fruit, Mucuna pruriens (Velvet bean), Chunghyuldan (CHD), Paeoniae Alba Radix. The present review may be beneficial for designing future drugs for effective treatment of PD.
    Matched MeSH terms: Parkinson Disease/drug therapy*
  2. Modeling Parkinson's Disease in Zebrafish
    Najib NHM, Nies YH, Abd Halim SAS, Yahaya MF, Das S, Lim WL, et al.
    CNS Neurol Disord Drug Targets, 2020;19(5):386-399.
    PMID: 32640968 DOI: 10.2174/1871527319666200708124117
    Parkinson's Disease (PD) is one of the most common neurodegenerative disorders that affects the motor system, and includes cardinal motor symptoms such as resting tremor, cogwheel rigidity, bradykinesia and postural instability. Its prevalence is increasing worldwide due to the increase in life span. Although, two centuries since the first description of the disease, no proper cure with regard to treatment strategies and control of symptoms could be reached. One of the major challenges faced by the researchers is to have a suitable research model. Rodents are the most common PD models used, but no single model can replicate the true nature of PD. In this review, we aim to discuss another animal model, the zebrafish (Danio rerio), which is gaining popularity. Zebrafish brain has all the major structures found in the mammalian brain, with neurotransmitter systems, and it also possesses a functional blood-brain barrier similar to humans. From the perspective of PD research, the zebrafish possesses the ventral diencephalon, which is thought to be homologous to the mammalian substantia nigra. We summarize the various zebrafish models available to study PD, namely chemical-induced and genetic models. The zebrafish can complement the use of other animal models for the mechanistic study of PD and help in the screening of new potential therapeutic compounds.
    Matched MeSH terms: Parkinson Disease/drug therapy*
  3. miR-124 and Parkinson's disease: A biomarker with therapeutic potential
    Angelopoulou E, Paudel YN, Piperi C
    Pharmacol Res, 2019 12;150:104515.
    PMID: 31707035 DOI: 10.1016/j.phrs.2019.104515
    Parkinson's disease (PD) is a multifactorial disorder, attributed to a complex interplay between genetic and epigenetic factors. Although the exact etiology of the disease remains elusive, dysregulation of signaling pathways implicated in cell survival, apoptosis, protein aggregation, mitochondrial dysfunction, autophagy, oxidative damage and neuroinflammation, contributes to its pathogenesis. MicroRNAs (miRs) are endogenous short non-coding RNA molecules that negatively regulate gene expression at a post-transcriptional level. MiR-124 is one of the most abundantly expressed miRs in the brain that participates in neurogenesis, synapse morphology, neurotransmission, inflammation, autophagy and mitochondrial function. Accumulating pre-clinical evidence shows that miR-124 may act through calpain 1/p25/cyclin-dependent kinases 5 (CDK5), nuclear factor-kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), Bcl-2-interacting mediator of cell death (Bim), 5' adenosine monophosphate-activated protein kinase (AMPK) and extracellular signal-regulated kinase (ERK)-mediated pathways to regulate cell survival, apoptosis, autophagy, mitochondrial dysfunction, oxidative damage and neuroinflammation in PD. Moreover, clinical evidence indicates that reduced plasma miR-124 levels may serve as a potential diagnostic biomarker in PD. This review provides an update of the pathogenic implication of miR-124 activity in PD and discusses its targeting potential for the development of future therapeutic strategies.
    Matched MeSH terms: Parkinson Disease/drug therapy
  4. Plant Polyphenols as Neuroprotective Agents in Parkinson's Disease Targeting Oxidative Stress
    Hor SL, Teoh SL, Lim WL
    Curr Drug Targets, 2020;21(5):458-476.
    PMID: 31625473 DOI: 10.2174/1389450120666191017120505
    Parkinson's disease (PD) is the second most prevalent progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the human midbrain. Various ongoing research studies are competing to understand the pathology of PD and elucidate the mechanisms underlying neurodegeneration. Current pharmacological treatments primarily focused on improving dopamine metabolism in PD patients, despite the side effects of long-term usage. In recent years, it is recognized that oxidative stress-mediated pathways lead to neurodegeneration in the brain, which is associated with the pathophysiology of PD. The importance of oxidative stress is often less emphasized when developing potential therapeutic approaches. Natural plant antioxidants have been shown to mediate the oxidative stress-induced effects in PD, which has gained considerable attention in both in vitro and in vivo studies. Yet, clinical trials on natural polyphenol compounds are limited, restricting the potential use of these compounds as an alternative treatment for PD. Therefore, this review provides an understanding of the oxidative stress-induced effects in PD by elucidating the underlying events contributing to oxidative stress and explore the potential use of polyphenols in improving the oxidative status in PD. Preclinical findings have supported the potential of polyphenols in providing neuroprotection against oxidative stress-induced toxicity in PD. However, limiting factors, such as safety and bioavailability of polyphenols, warrant further investigations so as to make them the potential target for clinical applications in the treatment and management of PD.
    Matched MeSH terms: Parkinson Disease/drug therapy*
  5. Pharmacology and toxicology of α- and β-Asarone: A review of preclinical evidence
    Chellian R, Pandy V, Mohamed Z
    Phytomedicine, 2017 Aug 15;32:41-58.
    PMID: 28732807 DOI: 10.1016/j.phymed.2017.04.003
    BACKGROUND: Asarone is one of the most researched phytochemicals and is mainly present in the Acorus species and Guatteria gaumeri Greenman. In preclinical studies, both α- and β-asarone have been reported to have numerous pharmacological activities and at the same time, many studies have also revealed the toxicity of α- and β-asarone.

    PURPOSE: The purpose of this comprehensive review is to compile and analyze the information related to the pharmacokinetic, pharmacological, and toxicological studies reported on α- and β-asarone using preclinical in vitro and in vivo models. Besides, the molecular targets and mechanism(s) involved in the biological activities of α- and β-asarone were discussed.

    METHODS: Databases including PubMed, ScienceDirect and Google scholar were searched and the literature from the year 1960 to January 2017 was retrieved using keywords such as α-asarone, β-asarone, pharmacokinetics, toxicology, pharmacological activities (e.g. depression, anxiety).

    RESULTS: Based on the data obtained from the literature search, the pharmacokinetic studies of α- and β-asarone revealed that their oral bioavailability in rodents is poor with a short plasma half-life. Moreover, the metabolism of α- and β-asarone occurs mainly through cytochrome-P450 pathways. Besides, both α- and/or β-asarone possess a wide range of pharmacological activities such as antidepressant, antianxiety, anti-Alzheimer's, anti-Parkinson's, antiepileptic, anticancer, antihyperlipidemic, antithrombotic, anticholestatic and radioprotective activities through its interaction with multiple molecular targets. Importantly, the toxicological studies revealed that both α- and β-asarone can cause hepatomas and might possess mutagenicity, genotoxicity, and teratogenicity.

    CONCLUSIONS: Taken together, further preclinical studies are required to confirm the pharmacological properties of α-asarone against depression, anxiety, Parkinson's disease, psychosis, drug dependence, pain, inflammation, cholestasis and thrombosis. Besides, the anticancer effect of β-asarone should be further studied in different types of cancers using in vivo models. Moreover, further dose-dependent in vivo studies are required to confirm the toxicity of α- and β-asarone. Overall, this extensive review provides a detailed information on the preclinical pharmacological and toxicological activities of α-and β-asarone and this could be very useful for researchers who wish to conduct further preclinical studies using α- and β-asarone.

    Matched MeSH terms: Parkinson Disease/drug therapy
  6. The current status of pharmacotherapy for the treatment of Parkinson's disease: transition from single-target to multitarget therapy
    Cheong SL, Federico S, Spalluto G, Klotz KN, Pastorin G
    Drug Discov Today, 2019 09;24(9):1769-1783.
    PMID: 31102728 DOI: 10.1016/j.drudis.2019.05.003
    Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons. Motor features such as tremor, rigidity, bradykinesia and postural instability are common traits of PD. Current treatment options provide symptomatic relief to the condition but are unable to reverse disease progression. The conventional single-target therapeutic approach might not always induce the desired effect owing to the multifactorial nature of PD. Hence, multitarget strategies have been proposed to simultaneously target multiple proteins involved in the development of PD. Herein, we provide an overview of the pathogenesis of PD and the current pharmacotherapies. Furthermore, rationales and examples of multitarget approaches that have been tested in preclinical trials for the treatment of PD are also discussed.
    Matched MeSH terms: Parkinson Disease/drug therapy*
  7. Role of Liver Growth Factor (LGF) in Parkinson's Disease: Molecular Insights and Therapeutic Opportunities
    Angelopoulou E, Paudel YN, Piperi C
    Mol Neurobiol, 2021 Jul;58(7):3031-3042.
    PMID: 33608826 DOI: 10.1007/s12035-021-02326-9
    Parkinson's disease is the most common neurodegenerative movement disorder with unclear etiology and only symptomatic treatment to date. Toward the development of novel disease-modifying agents, neurotrophic factors represent a reasonable and promising therapeutic approach. However, despite the robust preclinical evidence, clinical trials using glial-derived neurotrophic factor (GDNF) and neurturin have been unsuccessful. In this direction, the therapeutic potential of other trophic factors in PD and the elucidation of the underlying molecular mechanisms are of paramount importance. The liver growth factor (LGF) is an albumin-bilirubin complex acting as a hepatic mitogen, which also exerts regenerative effects on several extrahepatic tissues including the brain. Accumulating evidence suggests that intracerebral and peripheral administration of LGF can enhance the outgrowth of nigrostriatal dopaminergic axonal terminals; promote the survival, migration, and differentiation of neuronal stem cells; and partially protect against dopaminergic neuronal loss in the substantia nigra of PD animal models. In most studies, these effects are accompanied by improved motor behavior of the animals. Potential underlying mechanisms involve transient microglial activation, TNF-α upregulation, and activation of the extracellular signal-regulated kinases 1/2 (ERK1/2) and of the transcription factor cyclic AMP response-element binding protein (CREB), along with anti-inflammatory and antioxidant pathways. Herein, we summarize recent preclinical evidence on the potential role of LGF in PD pathogenesis, aiming to shed more light on the underlying molecular mechanisms and reveal novel therapeutic opportunities for this debilitating disease.
    Matched MeSH terms: Parkinson Disease/drug therapy*
  8. Impulsive-compulsive behaviors are common in Asian Parkinson's disease patients: assessment using the QUIP
    Lim SY, Tan ZK, Ngam PI, Lor TL, Mohamed H, Schee JP, et al.
    Parkinsonism Relat Disord, 2011 Dec;17(10):761-4.
    PMID: 21839665 DOI: 10.1016/j.parkreldis.2011.07.009
    There are limited data on the prevalence of impulsive-compulsive behaviors and subsyndromal impulsive-compulsive behaviors in Asian patients with Parkinson's disease, who are treated with lower dosages of dopaminergic medications.
    Matched MeSH terms: Parkinson Disease/drug therapy
  9. Asian perspectives on the recognition and management of levodopa 'wearing-off' in Parkinson's disease
    Bhidayasiri R, Hattori N, Jeon B, Chen RS, Lee MK, Bajwa JA, et al.
    Expert Rev Neurother, 2015;15(11):1285-97.
    PMID: 26390066 DOI: 10.1586/14737175.2015.1088783
    Most Parkinson's disease patients will receive levodopa therapy, and of these, the majority will develop some levodopa-induced complications. For many patients, the first complication to develop is the decline in the duration of therapeutic benefit of each levodopa dose, a phenomenon commonly termed 'wearing-off'. There is already extensive literature documenting the epidemiology and management of wearing-off in Parkinson's disease patients of western descent. However, data derived from these studies might not always apply to patients of Asian descent due to genetic variations, differences in co-morbidities or non-availability of certain drugs. This review summarizes the current literature regarding the epidemiology of wearing-off in Asian (including Arab) patients and discusses the management issues in the context of drug availability in Asia.
    Matched MeSH terms: Parkinson Disease/drug therapy*
  10. Quantitative Structure-Activity Relationship (QSAR) Studies for the Inhibition of MAOs
    Ramesh M, Muthuraman A
    Comb Chem High Throughput Screen, 2020;23(9):887-897.
    PMID: 32208114 DOI: 10.2174/1386207323666200324173231
    Monoamine oxidases are the crucial drug targets for the treatment of neurodegenerative disorders like depression, Parkinson's disease, and Alzheimer's disease. The enzymes catalyze the oxidative deamination of several monoamine containing neurotransmitters, i.e. serotonin (5-HT), melatonin, epinephrine, norepinephrine, phenylethylamine, benzylamine, dopamine, tyramine, etc. The oxidative reaction of monoamine oxidases results in the production of hydrogen peroxide that leads to the neurodegeneration process. Therefore, the inhibition of monoamine oxidases has shown a profound effect against neurodegenerative diseases. At present, the design and development of newer lead molecules for the inhibition of monoamine oxidases are under intensive research in the field of medicinal chemistry. Recently, the advancement in QSAR methodologies has shown considerable interest in the development of monoamine oxidase inhibitors. The present review describes the development of QSAR methodologies, and their role in the design of newer monoamine oxidase inhibitors. It will assist the medicinal chemist in the identification of selective and potent monoamine oxidase inhibitors from various chemical scaffolds.
    Matched MeSH terms: Parkinson Disease/drug therapy
  11. Interlink Between Insulin Resistance and Neurodegeneration with an Update on Current Therapeutic Approaches
    Bhattamisra SK, Shin LY, Saad HIBM, Rao V, Candasamy M, Pandey M, et al.
    CNS Neurol Disord Drug Targets, 2020;19(3):174-183.
    PMID: 32418534 DOI: 10.2174/1871527319666200518102130
    The interlink between diabetes mellitus and neurodegenerative diseases such as Alzheimer's Disease (AD) and Parkinson's Disease (PD) has been identified by several researchers. Patients with Type-2 Diabetes Mellitus (T2DM) are found to be affected with cognitive impairments leading to learning and memory deficit, while patients with Type-1 Diabetes Mellitus (T1DM) showed less severe levels of these impairments in the brain. This review aimed to discuss the connection between insulin with the pathophysiology of neurodegenerative diseases (AD and PD) and the current therapeutic approached mediated through insulin for management of neurodegenerative diseases. An extensive literature search was conducted using keywords "insulin"; "insulin resistance"; "Alzheimer's disease"; "Parkinson's disease" in public domains of Google scholar, PubMed, and ScienceDirect. Selected articles were used to construct this review. Studies have shown that impaired insulin signaling contributes to the accumulation of amyloid-β, neurofibrillary tangles, tau proteins and α-synuclein in the brain. Whereas, improvement in insulin signaling slows down the progression of cognitive decline. Various therapeutic approaches for altering the insulin function in the brain have been researched. Besides intranasal insulin, other therapeutics like PPAR-γ agonists, neurotrophins, stem cell therapy and insulin-like growth factor-1 are under investigation. Research has shown that insulin insensitivity in T2DM leads to neurodegeneration through mechanisms involving a variety of extracellular, membrane receptor, and intracellular signaling pathway disruptions. Some therapeutics, such as intranasal administration of insulin and neuroactive substances have shown promise but face problems related to genetic background, accessibility to the brain, and invasiveness of the procedures.
    Matched MeSH terms: Parkinson Disease/drug therapy
  12. Fulltext Rivastigmine: the advantages of dual inhibition of acetylcholinesterase and butyrylcholinesterase and its role in subcortical vascular dementia and Parkinson's disease dementia
    Kandiah N, Pai MC, Senanarong V, Looi I, Ampil E, Park KW, et al.
    Clin Interv Aging, 2017;12:697-707.
    PMID: 28458525 DOI: 10.2147/CIA.S129145
    Several studies have demonstrated clinical benefits of sustained cholinesterase inhibition with rivastigmine in Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). Unlike donepezil and galantamine that selectively inhibit acetylcholinesterase (AChE; EC 3.1.1.7), rivastigmine is a unique cholinesterase inhibitor with both AChE and butyrylcholinesterase (BuChE; EC 3.1.1.8) inhibitory activity. Rivastigmine is also available as transdermal patch that has been approved by the US Food and Drug Administration for the treatment of mild, moderate, and severe AD as well as mild-to-moderate PDD. In this review, we explore the role of BuChE inhibition in addition to AChE inhibition with rivastigmine in the outcomes of cognition, global function, behavioral symptoms, and activities of daily living. Additionally, we review the evidence supporting the use of dual AChE-BuChE inhibitory activity of rivastigmine as a therapeutic strategy in the treatment of neurological disorders, with a focus on the role of rivastigmine in subcortical dementias such as vascular dementia (VaD) and PDD. Toward this objective, we performed a literature search in PubMed and Ovid with limits to articles published in the English language before June 2016. The available evidence from the literature suggests that the dual inhibition of AChE and BuChE may afford additional therapeutic potential of rivastigmine in subcortical dementias (subcortical VaD and PDD) with benefits on cognition and behavioral symptoms. Rivastigmine was found to specifically benefit executive dysfunction frequently observed in subcortical dementias; however, large randomized clinical studies are warranted to support these observations.
    Matched MeSH terms: Parkinson Disease/drug therapy
  13. Earlier onset of motor complications in Parkinson's patients with comorbid diabetes mellitus
    Mohamed Ibrahim N, Ramli R, Koya Kutty S, Shah SA
    Mov Disord, 2018 12;33(12):1967-1968.
    PMID: 30427552 DOI: 10.1002/mds.27526
    Matched MeSH terms: Parkinson Disease/drug therapy*
  14. Emerging neuroprotective effect of metformin in Parkinson's disease: A molecular crosstalk
    Paudel YN, Angelopoulou E, Piperi C, Shaikh MF, Othman I
    Pharmacol Res, 2020 02;152:104593.
    PMID: 31843673 DOI: 10.1016/j.phrs.2019.104593
    Parkinson's disease (PD) is a devastating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and Lewy pathology. PD is a major concern of today's aging population and has emerged as a global health burden. Despite the rapid advances in PD research over the past decades, the gold standard therapy provides only symptomatic relief and fails to halt disease progression. Therefore, exploring novel disease-modifying therapeutic strategies is highly demanded. Metformin, which is currently used as a first-line therapy for type 2 diabetes mellitus (T2DM), has recently demonstrated to exert a neuroprotective role in several neurodegenerative disorders including PD, both in vitro and in vivo. In this review, we explore the neuroprotective potential of metformin based on emerging evidence from pre-clinical and clinical studies. Regarding the underlying molecular mechanisms, metformin has been shown to inhibit α-synuclein (SNCA) phosphorylation and aggregation, prevent mitochondrial dysfunction, attenuate oxidative stress, modulate autophagy mainly via AMP-activated protein kinase (AMPK) activation, as well as prevent neurodegeneration and neuroinflammation. Overall, the neuroprotective effects of metformin in PD pathogenesis present a novel promising therapeutic strategy that might overcome the limitations of current PD treatment.
    Matched MeSH terms: Parkinson Disease/drug therapy*
  15. Impact of the apelin/APJ axis in the pathogenesis of Parkinson's disease with therapeutic potential
    Angelopoulou E, Paudel YN, Bougea A, Piperi C
    J Neurosci Res, 2021 Sep;99(9):2117-2133.
    PMID: 34115895 DOI: 10.1002/jnr.24895
    The pathogenesis of Parkinson's disease (PD) remains elusive. There is still no available disease-modifying strategy against PD, whose management is mainly symptomatic. A growing amount of preclinical evidence shows that a complex interplay between autophagy dysregulation, mitochondrial impairment, endoplasmic reticulum stress, oxidative stress, and excessive neuroinflammation underlies PD pathogenesis. Identifying key molecules linking these pathological cellular processes may substantially aid in our deeper understanding of PD pathophysiology and the development of novel effective therapeutic approaches. Emerging preclinical evidence indicates that apelin, an endogenous neuropeptide acting as a ligand of the orphan G protein-coupled receptor APJ, may play a key neuroprotective role in PD pathogenesis, via inhibition of apoptosis and dopaminergic neuronal loss, autophagy enhancement, antioxidant effects, endoplasmic reticulum stress suppression, as well as prevention of synaptic dysregulation in the striatum, excessive neuroinflammation, and glutamate-induced excitotoxicity. Underlying signaling pathways involve phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin, extracellular signal-regulated kinase 1/2, and inositol requiring kinase 1α/XBP1/C/EBP homologous protein. Herein, we discuss the role of apelin/APJ axis and associated molecular mechanisms on the pathogenesis of PD in vitro and in vivo and provide evidence for its challenging therapeutic potential.
    Matched MeSH terms: Parkinson Disease/drug therapy*
  16. Fulltext MPTP-induced mouse model of Parkinson's disease: A promising direction of therapeutic strategies
    Mustapha M, Mat Taib CN
    Bosn J Basic Med Sci, 2021 Aug 01;21(4):422-433.
    PMID: 33357211 DOI: 10.17305/bjbms.2020.5181
    Among the popular animal models of Parkinson's disease (PD) commonly used in research are those that employ neurotoxins, especially 1-methyl- 4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). This neurotoxin exerts it neurotoxicity by causing a barrage of insults, such as oxidative stress, mitochondrial apoptosis, inflammation, excitotoxicity, and formation of inclusion bodies acting singly and in concert, ultimately leading to dopaminergic neuronal damage in the substantia nigra pars compacta and striatum. The selective neurotoxicity induced by MPTP in the nigrostriatal dopaminergic neurons of the mouse brain has led to new perspectives on PD. For decades, the MPTP-induced mouse model of PD has been the gold standard in PD research even though it does not fully recapitulate PD symptomatology, but it does have the advantages of simplicity, practicability, affordability, and fewer ethical considerations and greater clinical correlation than those of other toxin models of PD. The model has rejuvenated PD research and opened new frontiers in the quest for more novel therapeutic and adjuvant agents for PD. Hence, this review summarizes the role of MPTP in producing Parkinson-like symptoms in mice and the experimental role of the MPTP-induced mouse model. We discussed recent developments of more promising PD therapeutics to enrich our existing knowledge about this neurotoxin using this model.
    Matched MeSH terms: Parkinson Disease/drug therapy*
  17. Glycogen synthase kinase-3 beta (GSK-3β) signaling: Implications for Parkinson's disease
    Golpich M, Amini E, Hemmati F, Ibrahim NM, Rahmani B, Mohamed Z, et al.
    Pharmacol Res, 2015 Jul;97:16-26.
    PMID: 25829335 DOI: 10.1016/j.phrs.2015.03.010
    Glycogen synthase kinase 3 (GSK-3) dysregulation plays an important role in the pathogenesis of numerous disorders, affecting the central nervous system (CNS) encompassing both neuroinflammation and neurodegenerative diseases. Several lines of evidence have illustrated a key role of the GSK-3 and its cellular and molecular signaling cascades in the control of neuroinflammation. Glycogen synthase kinase 3 beta (GSK-3β), one of the GSK-3 isomers, plays a major role in neuronal apoptosis and its inhibition decreases expression of alpha-Synuclein (α-Synuclein), which make this kinase an attractive therapeutic target for neurodegenerative disorders. Parkinson's disease (PD) is a chronic neurodegenerative movement disorder characterized by the progressive and massive loss of dopaminergic neurons by neuronal apoptosis in the substantia nigra pars compacta and depletion of dopamine in the striatum, which lead to pathological and clinical abnormalities. Thus, understanding the role of GSK-3β in PD will enhance our knowledge of the basic mechanisms underlying the pathogenesis of this disorder and facilitate the identification of new therapeutic avenues. In recent years, GSK-3β has been shown to play essential roles in modulating a variety of cellular functions, which have prompted efforts to develop GSK-3β inhibitors as therapeutics. In this review, we summarize GSK-3 signaling pathways and its association with neuroinflammation. Moreover, we highlight the interaction between GSK-3β and several cellular processes involved in the pathogenesis of PD, including the accumulation of α-Synuclein aggregates, oxidative stress and mitochondrial dysfunction. Finally, we discuss about GSK-3β inhibitors as a potential therapeutic strategy in PD.
    Matched MeSH terms: Parkinson Disease/drug therapy*
  18. Fractalkine (CX3CL1) signaling and neuroinflammation in Parkinson's disease: Potential clinical and therapeutic implications
    Angelopoulou E, Paudel YN, Shaikh MF, Piperi C
    Pharmacol Res, 2020 08;158:104930.
    PMID: 32445958 DOI: 10.1016/j.phrs.2020.104930
    Neuroinflammation plays a crucial role in the pathogenesis of Parkinson's disease (PD) with the dysregulation of microglial activity being tightly linked to dopaminergic degeneration. Fractalkine (CX3CL1), a chemokine mainly expressed by neurons, can modulate microglial activity through binding to its sole G-protein-coupled receptor (CX3CR1), expressed by microglia. Fractalkine/CX3CR1 signaling is one of the most important mediators of the communication between neurons and microglia, and its emerging role in neurodegenerative disorders including PD has been increasingly recognized. Pre-clinical evidence has revealed that fractalkine signaling axis exerts dual effects on PD-related inflammation and degeneration, which greatly depend on the isoform type (soluble or membrane-bound), animal model (mice or rats, toxin- or proteinopathy-induced), route of toxin administration, time course and specific brain region (striatum, substantia nigra). Furthermore, although existing clinical evidence is scant, it has been indicated that fractalkine may be possibly associated with PD progression, paving the way for future studies investigating its biomarker potential. In this review, we discuss recent evidence on the role of fractalkine/CX3CR1 signaling axis in PD pathogenesis, aiming to shed more light on the molecular mechanisms underlying the neuroinflammation commonly associated with the disease, as well as potential clinical and therapeutic implications.
    Matched MeSH terms: Parkinson Disease/drug therapy*
  19. Polar-phase indices of perioral muscle reciprocity during syllable production in Parkinson's disease
    Chu SY, Barlow SM, Lee J, Wang J
    Int J Speech Lang Pathol, 2017 12;19(6):616-627.
    PMID: 28425760 DOI: 10.1080/17549507.2016.1265587
    PURPOSE: This research characterised perioral muscle reciprocity and amplitude ratio in lower lip during bilabial syllable production [pa] at three rates to understand the neuromotor dynamics and scaling of motor speech patterns in individuals with Parkinson's disease (PD).

    METHOD: Electromyographic (EMG) signals of the orbicularis oris superior [OOS], orbicularis oris inferior [OOI] and depressor labii inferioris [DLI] were recorded during syllable production and expressed as polar-phase notations.

    RESULT: PD participants exhibited the general features of reciprocity between OOS, OOI and DLI muscles as reflected in the EMG during syllable production. The control group showed significantly higher integrated EMG amplitude ratio in the DLI:OOS muscle pairs than PD participants. No speech rate effects were found in EMG muscle reciprocity and amplitude magnitude across all muscle pairs.

    CONCLUSION: Similar patterns of muscle reciprocity in PD and controls suggest that corticomotoneuronal output to the facial nucleus and respective perioral muscles is relatively well-preserved in our cohort of mild idiopathic PD participants. Reduction of EMG amplitude ratio among PD participants is consistent with the putative reduction in the thalamocortical activation characteristic of this disease which limits motor cortex drive from generating appropriate commands which contributes to bradykinesia and hypokinesia of the orofacial mechanism.

    Matched MeSH terms: Parkinson Disease/drug therapy
  20. Levodopa-induced myocardial infarction in a patient with Parkinson's disease and severe coronary artery disease
    Ng CF, Tiau PW, Tan HJ, Norlinah MI
    J R Coll Physicians Edinb, 2019 Mar;49(1):37-39.
    PMID: 30838990 DOI: 10.4997/JRCPE.2019.108
    Levodopa is the most effective medical treatment for Parkinson's disease (PD) to date. As dopamine is known to increase cardiac inotropism and vasomotor tone, peripheral dopamine decarboxylase inhibitor is coadministered to suppress the peripheral conversion of levodopa to dopamine. Levodopa poses potential cardiovascular risks, thus its use in patients with existing coronary artery disease needs to be carefully monitored. We report a case of an elderly male with newly diagnosed PD who developed non-ST-elevation myocardial infarction following levodopa (Madopar) initiation.
    Matched MeSH terms: Parkinson Disease/drug therapy*
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