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Pharmaceutical Biology Dec 2019: Parkinson's disease (PD) is a neurodegenerative disorder due to gradual loss of dopaminergic nerves in the substantia nigra (SN) in the midbrain. PD leads to certain... (Review)
Review
: Parkinson's disease (PD) is a neurodegenerative disorder due to gradual loss of dopaminergic nerves in the substantia nigra (SN) in the midbrain. PD leads to certain motor disorders including resting tremor, muscle stiffness and slow movement. Medicinal plants have shown positive pharmacological effects in treating different models of PD. Tendency to use natural products, especially plants, for the treatment of PD has been growing. This article reviews the basic aspects of medicinal plants and their bioactive compounds that could be used to treat PD. Reliable articles indexed in databases ISI, SID, PubMed, PubMed Central, Scopus and Web of Science were used. A total of 12 plant-derived active ingredients and 18 herbal extracts were included. Different compounds have so far been isolated from plants that affect PD especially by targeting pathways associated with the pathogenesis of the disease. Although some herbal extracts such as Hook. f. (Malvaceae), L. (Ginkgoaceae) L (Asteraceae) and certain active ingredients, such as berberine and curcumin, have shown positive effects in animal models of PD, potential active ingredients and mechanisms of action should be investigated in additional studies. Despite the wide variety of plants in the world, a limited number of them have been studied for anti-Parkinsonian activity, and therefore, there are numerous perspectives in this field for future studies on plants and their bioactive compounds.
Topics: Carthamus tinctorius; Ginkgo biloba; Hibiscus; Humans; Neuroprotective Agents; Parkinson Disease; Phytotherapy; Plant Preparations
PubMed: 31141426
DOI: 10.1080/13880209.2019.1618344 -
Parkinsonism & Related Disorders Apr 2020Parkinson's disease is a heterogeneous disorder with both motor and non-motor symptoms that contribute to functional impairment. To develop effective, disease modifying... (Review)
Review
Parkinson's disease is a heterogeneous disorder with both motor and non-motor symptoms that contribute to functional impairment. To develop effective, disease modifying treatments for these symptoms, biomarkers are necessary to detect neuropathological changes early in the disease course and monitor changes over time. Advances in MRI scan sequences and analytical techniques present numerous promising metrics to detect changes within the nigrostriatal system, implicated in the cardinal motor symptoms of the disease, and detect broader dysfunction involved in the non-motor symptoms, such as cognitive impairment. There is emerging evidence that iron sensitive, neuromelanin sensitive, diffusion sensitive, and resting state functional magnetic imaging measures can capture changes within the nigrostriatal system. Iron, neuromelanin, and diffusion sensitive measures demonstrate high specificity and sensitivity in distinguishing Parkinson's disease relative to controls, with inconsistent results differentiating Parkinson's disease relative to atypical parkinsonian disorders. They may also serve as useful monitoring biomarkers, with each possibly detecting different aspects of the disease course (early nigrosome changes versus broader substantia nigra changes). Investigations of non-motor symptoms, such as cognitive impairment, require careful consideration of the nature of cognitive deficits to characterize regional and network specific impairment. While the early, executive dysfunction observed is consistent with nigrostriatal degeneration, the memory and visuospatial impairments, the harbingers of a dementia process reflect dopaminergic independent dysfunction involving broader regions of the brain.
Topics: Biomarkers; Brain; Cognitive Dysfunction; Humans; Magnetic Resonance Imaging; Parkinson Disease; Striatonigral Degeneration
PubMed: 31629653
DOI: 10.1016/j.parkreldis.2019.10.002 -
CNS Neuroscience & Therapeutics Mar 2021Studies regarding the impact of Parkinson's disease (PD) on quality of life (QOL) have reported conflicting results, and the underlying QOL domains require further... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Studies regarding the impact of Parkinson's disease (PD) on quality of life (QOL) have reported conflicting results, and the underlying QOL domains require further study. In order to understand the association between PD and QOL, we conducted this meta-analysis to systematically compare QOL between PD patients and healthy controls.
METHOD
The PubMed, PsycINFO, EMBASE, and Web of Science databases were systematically searched. Data were analyzed using the random-effects model.
RESULTS
Twenty studies covering 2707 PD patients and 150,661 healthy controls were included in the study. Compared with healthy controls, PD patients had significantly poorer QOL overall and in most domains with moderate to large effects sizes. Different QOL measures varied in their association with quality of life, with the Parkinson's Disease Questionnaire-39 (PDQ-39) having the largest effect size (standard mean difference, SMD = -1.384, 95% CI: -1.607, -1.162, Z = 12.189, P < 0.001), followed by the Europe Quality of Life Questionnaire-visual analogue scale (EQ-VAS) (SMD = -1.081, 95% CI: -1.578, -0.584, Z = -4.265, P < 0.001), Europe Quality of Life Questionnaire-5D (EQ-5D) (SMD = -0.889, 95% CI: -1.181, -0.596, Z = -5.962, P < 0.001), and the Short-form Health Survey (SF) scales (physical dimension: SMD = -0.826, 95% CI: -1.529, -0.123, Z = -2.303, P = 0.021; mental dimension: SMD = -0.376, 95% CI: -0.732, -0.019, Z = -2.064, P = 0.039).
CONCLUSION
PD patients had lower QOL compared with healthy controls in most domains, especially in physical function and mental health. Considering the negative impact of poor QOL on daily life and functional outcomes, effective measures should be developed to improve QOL in this population.
Topics: Case-Control Studies; Cross-Sectional Studies; Humans; Parkinson Disease; Quality of Life
PubMed: 33372386
DOI: 10.1111/cns.13549 -
Acta Neuropathologica May 2023Extracellular vesicles (EVs), including exosomes, microvesicles, and oncosomes, are nano-sized particles enclosed by a lipid bilayer. EVs are released by virtually all... (Review)
Review
Extracellular vesicles (EVs), including exosomes, microvesicles, and oncosomes, are nano-sized particles enclosed by a lipid bilayer. EVs are released by virtually all eukaryotic cells and have been shown to contribute to intercellular communication by transporting proteins, lipids, and nucleic acids. In the context of neurodegenerative diseases, EVs may carry toxic, misfolded forms of amyloidogenic proteins and facilitate their spread to recipient cells in the central nervous system (CNS). CNS-originating EVs can cross the blood-brain barrier into the bloodstream and may be found in other body fluids, including saliva, tears, and urine. EVs originating in the CNS represent an attractive source of biomarkers for neurodegenerative diseases, because they contain cell- and cell state-specific biological materials. In recent years, multiple papers have reported the use of this strategy for identification and quantitation of biomarkers for neurodegenerative diseases, including Parkinson's disease and atypical parkinsonian disorders. However, certain technical issues have yet to be standardized, such as the best surface markers for isolation of cell type-specific EVs and validating the cellular origin of the EVs. Here, we review recent research using CNS-originating EVs for biomarker studies, primarily in parkinsonian disorders, highlight technical challenges, and propose strategies for overcoming them.
Topics: Humans; Extracellular Vesicles; Central Nervous System; Exosomes; Neurodegenerative Diseases; Parkinson Disease; Biomarkers
PubMed: 37012443
DOI: 10.1007/s00401-023-02557-1 -
Neuromodulation : Journal of the... Jul 2021Freezing of gait (FoG) is one of the most disabling yet poorly understood symptoms of Parkinson's disease (PD). FoG is an episodic gait pattern characterized by the... (Review)
Review
INTRODUCTION
Freezing of gait (FoG) is one of the most disabling yet poorly understood symptoms of Parkinson's disease (PD). FoG is an episodic gait pattern characterized by the inability to step that occurs on initiation or turning while walking, particularly with perception of tight surroundings. This phenomenon impairs balance, increases falls, and reduces the quality of life.
MATERIALS AND METHODS
Clinical-anatomical correlations, electrophysiology, and functional imaging have generated several mechanistic hypotheses, ranging from the most distal (abnormal central pattern generators of the spinal cord) to the most proximal (frontal executive dysfunction). Here, we review the neuroanatomy and pathophysiology of gait initiation in the context of FoG, and we discuss targets of central nervous system neuromodulation and their outcomes so far. The PubMed database was searched using these key words: neuromodulation, freezing of gait, Parkinson's disease, and gait disorders.
CONCLUSION
Despite these investigations, the pathogenesis of this process remains poorly understood. The evidence presented in this review suggests FoG to be a heterogenous phenomenon without a single unifying pathologic target. Future studies rigorously assessing targets as well as multimodal approaches will be essential to define the next generation of therapeutic treatments.
Topics: Gait; Gait Disorders, Neurologic; Humans; Parkinson Disease; Quality of Life; Walking
PubMed: 33368872
DOI: 10.1111/ner.13347 -
Journal of Parkinson's Disease 2021Human genetic studies as well as studies in animal models indicate that lysosomal dysfunction plays a key role in the pathogenesis of Parkinson's disease. Among the... (Review)
Review
Human genetic studies as well as studies in animal models indicate that lysosomal dysfunction plays a key role in the pathogenesis of Parkinson's disease. Among the lysosomal genes involved, GBA1 has the largest impact on Parkinson's disease risk. Deficiency in the GBA1 encoded enzyme glucocerebrosidase (GCase) leads to the accumulation of the GCase glycolipid substrates glucosylceramide and glucosylsphingosine and ultimately results in toxicity and inflammation and negatively affect many clinical aspects of Parkinson's disease, including disease risk, the severity of presentation, age of onset, and likelihood of progression to dementia. These findings support the view that re-establishing normal levels of GCase enzyme activity may reduce the progression of Parkinson's disease in patients carrying GBA1 mutations. Studies in mouse models indicate that PR001, a AAV9 vector-based gene therapy designed to deliver a functional GBA1 gene to the brain, suggest that this therapeutic approach may slow or stop disease progression. PR001 is currently being evaluated in clinical trials with Parkinson's disease patients carrying GBA1 mutations.
Topics: Animals; Gaucher Disease; Genetic Therapy; Glucosylceramidase; Humans; Lysosomes; Mice; Mutation; Parkinson Disease; alpha-Synuclein
PubMed: 34151863
DOI: 10.3233/JPD-212739 -
Biomolecules Jun 2020Biomarkers and disease-modifying therapies are both urgent unmet medical needs in the treatment of Parkinson's disease (PD) and must be developed concurrently because of... (Review)
Review
Biomarkers and disease-modifying therapies are both urgent unmet medical needs in the treatment of Parkinson's disease (PD) and must be developed concurrently because of their interdependent relationship: biomarkers for the early detection of disease (i.e., prior to overt neurodegeneration) are necessary in order for patients to receive maximal therapeutic benefit and vice versa; disease-modifying therapies must become available for patients whose potential for disease diagnosis and prognosis can be predicted with biomarkers. This review provides an overview of the milestones achieved to date in the therapeutic strategy development of disease-modifying therapies and biomarkers for PD, with a focus on the most common and advanced genetically linked targets alpha-synuclein (), leucine-rich repeat kinase-2 () and glucocerebrosidase (. Furthermore, we discuss the convergence of the different pathways and the importance of patient stratification and how these advances may apply more broadly to idiopathic PD. The heterogeneity of PD poses a challenge for therapeutic and biomarker development, however, the one gene- one target approach has brought us closer than ever before to an unprecedented number of clinical trials and biomarker advancements.
Topics: Animals; Biomarkers; Genetic Heterogeneity; Genetic Therapy; History, 21st Century; Humans; Molecular Targeted Therapy; Mutation; Parkinson Disease
PubMed: 32560161
DOI: 10.3390/biom10060912 -
Tidsskrift For Den Norske Laegeforening... May 2023Parkinsonism can have many causes, among them cerebrovascular disease. Vascular parkinsonism can be caused by infarction or haemorrhage in the nigrostriatal pathway,...
Parkinsonism can have many causes, among them cerebrovascular disease. Vascular parkinsonism can be caused by infarction or haemorrhage in the nigrostriatal pathway, resulting in hemiparkinsonism, or by widespread small vessel disease in the white matter, leading to the gradual development of bilateral symptoms in the lower extremities. Compared to patients with Parkinson's disease, individuals with vascular parkinsonism have earlier onset of gait disturbance, are more likely to have urinary incontinence and cognitive impairment, and have poorer treatment response and prognosis; however, they are less likely to have tremor. With its unclear pathophysiology, varying clinical picture and overlap with other diseases, vascular parkinsonism remains a little known and somewhat controversial diagnosis.
Topics: Humans; Parkinson Disease; Parkinsonian Disorders; Cerebrovascular Disorders; Vascular Diseases; Tremor
PubMed: 37158514
DOI: 10.4045/tidsskr.22.0539 -
International Journal of Molecular... Oct 2022The bidirectional interaction between the gut microbiota (GM) and the Central Nervous System, the so-called gut microbiota brain axis (GMBA), deeply affects brain... (Review)
Review
The bidirectional interaction between the gut microbiota (GM) and the Central Nervous System, the so-called gut microbiota brain axis (GMBA), deeply affects brain function and has an important impact on the development of neurodegenerative diseases. In Parkinson's disease (PD), gastrointestinal symptoms often precede the onset of motor and non-motor manifestations, and alterations in the GM composition accompany disease pathogenesis. Several studies have been conducted to unravel the role of dysbiosis and intestinal permeability in PD onset and progression, but the therapeutic and diagnostic applications of GM modifying approaches remain to be fully elucidated. After a brief introduction on the involvement of GMBA in the disease, we present evidence for GM alterations and leaky gut in PD patients. According to these data, we then review the potential of GM-based signatures to serve as disease biomarkers and we highlight the emerging role of probiotics, prebiotics, antibiotics, dietary interventions, and fecal microbiota transplantation as supportive therapeutic approaches in PD. Finally, we analyze the mutual influence between commonly prescribed PD medications and gut-microbiota, and we offer insights on the involvement also of nasal and oral microbiota in PD pathology, thus providing a comprehensive and up-to-date overview on the role of microbial features in disease diagnosis and treatment.
Topics: Humans; Gastrointestinal Microbiome; Parkinson Disease; Dysbiosis; Anti-Bacterial Agents; Biomarkers
PubMed: 36293176
DOI: 10.3390/ijms232012289 -
Translational Neurodegeneration Jul 2023Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. More than 200 years after its first clinical... (Review)
Review
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. More than 200 years after its first clinical description, PD remains a serious affliction that affects a growing proportion of the population. Prevailing treatments only alleviate symptoms; there is still neither a cure that targets the neurodegenerative processes nor therapies that modify the course of the disease. Over the past decades, several animal models have been developed to study PD. Although no model precisely recapitulates the pathology, they still provide valuable information that contributes to our understanding of the disease and the limitations of our treatment options. This review comprehensively summarizes the different animal models available for Parkinson's research, with a focus on those induced by drugs, neurotoxins, pesticides, genetic alterations, α-synuclein inoculation, and viral vector injections. We highlight their characteristics and ability to reproduce PD-like phenotypes. It is essential to realize that the strengths and weaknesses of each model and the induction technique at our disposal are determined by the research question being asked. Our review, therefore, seeks to better aid researchers by ensuring a concrete discernment of classical and novel animal models in PD research.
Topics: Animals; Parkinson Disease; Disease Models, Animal; Neurotoxins; Mutation
PubMed: 37468944
DOI: 10.1186/s40035-023-00368-8