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Gastrointestinal Dysfunction in Parkinson's Disease.
Safarpour, D, Sharzehi, K, Pfeiffer, RF
Drugs. 2022;(2):169-197
Abstract
There has been exponential growth in the awareness and understanding of gastrointestinal (GI) dysfunction in Parkinson's disease (PD) over the past 3 decades. The clinical features of GI dysfunction in PD have been clearly identified and innovative research has demonstrated the presence of pathology within the enteric nervous system (ENS) in individuals with PD, leading to suggestions that the GI system may be ground zero for the genesis and the portal of entry of PD pathology, which then ascends via the vagus nerve to the central nervous system (CNS). This theory, as well as the more recent recognition of the association of PD with dysbiosis within the gut microbiota, has been the object of intense study and scrutiny. Since most PD medications are absorbed through the GI system, the need for better understanding of changes within the GI tract that may potentially affect the pattern of response to medications has become evident. In this review, current knowledge of the pathophysiology of changes within the GI tract and the gut microbiome of individuals with PD, including changes that occur with progression of the disease, will be addressed. We focus on common clinical GI problems in PD that can arise from different segments of the GI tract. Relevant diagnostic evaluations and treatment options for each of these problems will be reviewed.
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Imaging the Substantia Nigra in Parkinson Disease and Other Parkinsonian Syndromes.
Bae, YJ, Kim, JM, Sohn, CH, Choi, JH, Choi, BS, Song, YS, Nam, Y, Cho, SJ, Jeon, B, Kim, JH
Radiology. 2021;(2):260-278
Abstract
Parkinson disease is characterized by dopaminergic cell loss in the substantia nigra of the midbrain. There are various imaging markers for Parkinson disease. Recent advances in MRI have enabled elucidation of the underlying pathophysiologic changes in the nigral structure. This has contributed to accurate and early diagnosis and has improved disease progression monitoring. This article aims to review recent developments in nigral imaging for Parkinson disease and other parkinsonian syndromes, including nigrosome imaging, neuromelanin imaging, quantitative iron mapping, and diffusion-tensor imaging. In particular, this article examines nigrosome imaging using 7-T MRI and 3-T susceptibility-weighted imaging. Finally, this article discusses volumetry and its clinical importance related to symptom manifestation. This review will improve understanding of recent advancements in nigral imaging of Parkinson disease. Published under a CC BY 4.0 license.
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Role of luteolin in overcoming Parkinson's disease.
Siddique, YH
BioFactors (Oxford, England). 2021;(2):198-206
Abstract
Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting elderly people (>60 years old) worldwide. There is no permanent cure for the disease but the symptomatic relief can be obtained by using dopamine agonists besides L-dopa therapy. The longer use of the drugs is associated with several side effects. Hence, the researchers have made a considerable attention toward the development of neuroprotective agents from plants. A number of phytochemicals have been demonstrated for their protective effects in various in vitro, in vivo, and clinical studies. In this context, luteolin, a flavone which is present in fruits and vegetables has been attributed to a number of pharmacological properties including neuroprotective. The present review demonstrates the bioavailability, oral absorption, and mechanism of action against PD.
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Nanotechnology Driven Approaches for the Management of Parkinson's Disease: Current Status and Future Perspectives.
Sharma, S, Rabbani, SA, Agarwal, T, Baboota, S, Pottoo, FH, Kadian, R
Current drug metabolism. 2021;(4):287-298
Abstract
Parkinson's disease (PD) is believed to be one of the commonly found adult-onset movement disorder occurring due to neurodegeneration and striatal dopamine deficiency. Although clinical diagnosis depends on the occurrence of bradykinesia and other cardinal motor features, PD is linked with many non-motor symptoms that are responsible for overall disability. Among several factors, genetic and environment-related factors are thought to be the major ones accountable for PD. Comprehensive research has shown that a number of drugs are effective in providing symptomatic relief to the patients suffering from PD. But some drug molecules suffer from significant drawbacks such as poor bioavailability and instability, therefore, they sometimes fail to deliver the expected results. Hence, to resolve these issues, new promising novel drug delivery systems have been developed. Liposomes, solid lipid nanoparticles, nanoemulsion, self-emulsifying drug delivery system (SEDDS), niosomes are some of the novel drug delivery system (NDDS) carriers that have been explored for enhancing the CNS concentration of levodopa, apomorphine, resveratrol, and other numerous drugs. This paper elucidates various drugs that have been studied for their potential contribution to the treatment and management of PD and also reviews and acknowledges the efforts of several scientists who successfully established various NDDS approaches for these drugs for the management of PD.
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Emerging Neuroimaging Biomarkers Across Disease Stage in Parkinson Disease: A Review.
Mitchell, T, Lehéricy, S, Chiu, SY, Strafella, AP, Stoessl, AJ, Vaillancourt, DE
JAMA neurology. 2021;(10):1262-1272
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Abstract
IMPORTANCE Imaging biomarkers in Parkinson disease (PD) are increasingly important for monitoring progression in clinical trials and also have the potential to improve clinical care and management. This Review addresses a critical need to make clear the temporal relevance for diagnostic and progression imaging biomarkers to be used by clinicians and researchers over the clinical course of PD. Magnetic resonance imaging (diffusion imaging, neuromelanin-sensitive imaging, iron-sensitive imaging, T1-weighted imaging), positron emission tomography/single-photon emission computed tomography dopaminergic, serotonergic, and cholinergic imaging as well as metabolic and cerebral blood flow network neuroimaging biomarkers in the preclinical, prodromal, early, and moderate to late stages are characterized. OBSERVATIONS If a clinical trial is being carried out in the preclinical and prodromal stages, potentially useful disease-state biomarkers include dopaminergic imaging of the striatum; metabolic imaging; free-water, neuromelanin-sensitive, and iron-sensitive imaging in the substantia nigra; and T1-weighted structural magnetic resonance imaging. Disease-state biomarkers that can distinguish atypical parkinsonisms are metabolic imaging, free-water imaging, and T1-weighted imaging; dopaminergic imaging and other molecular imaging track progression in prodromal patients, whereas other established progression biomarkers need to be evaluated in prodromal cohorts. Progression in early-stage PD can be monitored using dopaminergic imaging in the striatum, metabolic imaging, and free-water and neuromelanin-sensitive imaging in the posterior substantia nigra. Progression in patients with moderate to late-stage PD can be monitored using free-water imaging in the anterior substantia nigra, R2* of substantia nigra, and metabolic imaging. Cortical thickness and gyrification might also be useful markers or predictors of progression. Dopaminergic imaging and free-water imaging detect progression over 1 year, whereas other modalities detect progression over 18 months or longer. The reliability of progression biomarkers varies with disease stage, whereas disease-state biomarkers are relatively consistent in individuals with preclinical, prodromal, early, and moderate to late-stage PD. CONCLUSIONS AND RELEVANCE Imaging biomarkers for various stages of PD are readily available to be used as outcome measures in clinical trials and are potentially useful in multimodal combination with routine clinical assessment. This Review provides a critically important template for considering disease stage when implementing diagnostic and progression biomarkers in both clinical trials and clinical care settings.
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Digital Therapeutics in Parkinson's Disease: Practical Applications and Future Potential.
Ellis, TD, Earhart, GM
Journal of Parkinson's disease. 2021;(s1):S95-S101
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Abstract
Digital therapeutics, treatments delivered remotely and enabled by modern technology, facilitate the provision of personalized, evidence-based, interdisciplinary interventions to manage the complexities associated with Parkinson's disease. In the context of the COVID-19 pandemic, the need for digital therapeutics has arguably never been greater. However, despite new advances in technology and a heightened interest due to the pandemic, digital therapeutics remain underdeveloped and underutilized. In this paper, we briefly review practical applications and emerging advances in digital therapeutic platforms that target motor and non-motor signs and healthy lifestyle behaviors such as regular exercise, a healthful diet and optimal sleep hygiene habits. Future applications which could transform personalized self-management and patient care are presented. Opportunities, drawbacks and barriers to access are discussed.
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Foods with Potential Prooxidant and Antioxidant Effects Involved in Parkinson's Disease.
Miranda-Díaz, AG, García-Sánchez, A, Cardona-Muñoz, EG
Oxidative medicine and cellular longevity. 2020;:6281454
Abstract
Oxidative stress plays a fundamental role in the pathogenesis of Parkinson's disease (PD). Oxidative stress appears to be responsible for the gradual dysfunction that manifests via numerous cellular pathways throughout PD progression. This review will describe the prooxidant effect of excessive consumption of processed food. Processed meat can affect health due to its high sodium content, advanced lipid oxidation end-products, cholesterol, and free fatty acids. During cooking, lipids can react with proteins to form advanced end-products of lipid oxidation. Excessive consumption of different types of carbohydrates is a risk factor for PD. The antioxidant effects of some foods in the regular diet provide an inconclusive interpretation of the environment's mechanisms with the modulation of oxidation stress-induced PD. Some antioxidant molecules are known whose primary mechanism is the neuroprotective effect. The melatonin mechanism consists of neutralizing reactive oxygen species (ROS) and inducing antioxidant enzyme's expression and activity. N-acetylcysteine protects against the development of PD by restoring levels of brain glutathione. The balanced administration of vitamin B3, ascorbic acid, vitamin D and the intake of caffeine every day seem beneficial for brain health in PD. Excessive chocolate intake could have adverse effects in PD patients. The findings reported to date do not provide clear benefits for a possible efficient therapeutic intervention by consuming the nutrients that are consumed regularly.
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αB-crystallin as a promising target in pathological conditions - A review.
Maksimiuk, M, Sobiborowicz, A, Tuzimek, A, Deptała, A, Czerw, A, Badowska-Kozakiewicz, AM
Annals of agricultural and environmental medicine : AAEM. 2020;(3):326-334
Abstract
INTRODUCTION AND OBJECTIVE αB-crystallin belongs to the ubiquitous family of small heat-shock proteins. It was discovered as a physiological protein of the eye lens, maintaining its liquid-like property. Furthermore, αB-crystallin was proved to playa bipolar role in both physiological and pathophysiological conditions. This review discusses current knowledge about the biology and genetics of αB-crystallin, and summarizes recent advances in understanding its role in ophthalmic and neurological disorders, as well as breast cancer, renal cancer and other malignancies. STATE OF KNOWLEDGE α-crystallins are established as important elements of the protein quality control network, and consequently their defects are related to multiple human diseases. New studies highlight αB-crystallin's involvement in proliferative diabetic retinopathy angiogenesis and point out its therapeutic potential in age-related macular degeneration. αB-crystallin is thought to be associated with the disease-causing protein aggregates, leading to its connection with such neurological disturbances as anaplastic astrocytoma, Parkinson disease, aging deficits in the peripheral nervous system and multiple sclerosis. In breast cancer, it was proven to be a marker of aggressive behaviur and cerebral metastases. Strong expression of αB-crystallin promoted growth and migration of clear cell renal cell carcinoma cells and was correlated with lower overall survival rate. Considering other malignancies, its various roles were established in colorectal and gastric cancers, head and neck squamous cell carcinomas and osteosarcomas. CONCLUSIONS Further studies concerning αB-crystallin seem to be enormously promising, as they might improve our understanding of common human pathologies as well as contemporary diagnostics and treatment.
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Safinamide in the treatment of Parkinson's disease.
Müller, T
Neurodegenerative disease management. 2020;(4):195-204
Abstract
The deficiency pattern of neurotransmitters is heterogeneous in patients with Parkinson's disease. Consequence is an individual variable expression of motor and nonmotor features. They respond to agents with a broader spectrum of mode of actions, whereas dopamine substitution only targets impaired motor behavior. The pharmacological profile of safinamide includes reversible monoamine oxidase B inhibition and modulation of voltage-dependent sodium- and calcium channels with consecutive decline of glutamate release. Safinamide improves motor and nonmotor symptoms. Combination of safinamide with the catechol-O-methyltransferase inhibitor opicapone in one capsule is a promising future treatment alternative, which simplifies drug therapy in Parkinson's disease. Both agents complement each other in terms of application mode and efficacy on motor complications as adjuncts to levodopa therapy.
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An evaluation of subcutaneous apomorphine for the treatment of Parkinson's disease.
Müller, T
Expert opinion on pharmacotherapy. 2020;(14):1659-1665
Abstract
INTRODUCTION Heterogeneity of symptoms and individual variability of progression characterizes Parkinson's disease. Unmet therapeutic needs include a cure, disease modification, and improvement of available marketed dopamine-substituting compounds. Personalized treatment, tailored to the patients' needs and symptoms, aims to ameliorate impaired motor behavior and non-motor features. Injection or infusion of apomorphine is a therapeutic option for more advanced patients with severe levodopa associated motor complications. AREAS COVERED This narrative review summarizes the subcutaneous administration, efficacy, and side effects of the non-ergot derivative dopamine agonist apomorphine following a non-systematic literature research. EXPERT OPINION Subcutaneous apomorphine hydrochloride application rapidly terminates intervals with severe motor impairment with bolus injections. Oscillation of motor behavior well responds to continuous apomorphine infusions. Long-term application of the commercially available apomorphine hydrochloride solution sooner or later affects skin and oral mucosa. Onset of skin nodules associated with subcutaneous tissue inflammation probably results from the antioxidant preservative sodium metabisulfite in the apomorphine solution. Addition of another better tolerated and safer antioxidant instead of sodium metabisulphite or use of an already available concentrated apomorphine-free base formulation will enhance its future use, its tolerability, safety, and acceptance of subcutaneous and sublingual application.