scholarly journals Olfaction and Colour Vision: What Can They Tell Us about Parkinson’s Disease?

2018 ◽  
Vol 119 (2-3) ◽  
pp. 85-96 ◽  
Author(s):  
Irene Dall’Antonia ◽  
Karel Šonka ◽  
Petr Dušek
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Colour Vision ◽  
Neurodegenerative Disorder ◽  
Disease Onset ◽  
Alpha Synuclein ◽  
Nerve Tissue ◽  
Clinical Markers ◽  
Motor Abnormalities ◽  
Non Motor Symptoms

Parkinson’s disease is a neurodegenerative disorder with the pathological accumulation of alpha synuclein in the brain and peripheral nerve tissue. Early stages of synucleinopathies, often present clinically with rapid eye movement (REM) sleep disorder (RBD). Clinical markers that indicate early progression from RBD to manifest synucleinopathies include abnormal dopamine transporter (DAT) imaging, motor and non-motor symptoms. Despite the high diagnostic strength of DAT imaging and motor abnormalities, they are not the earliest biomarkers. Non-motor signs of neurodegeneration such as colour vision and olfaction abnormalities are detectable by clinical examination as early as 20 years before disease onset. Detailed analysis of olfactory and colour vision dysfunction can provide valuable information regarding brain pathologies, further specifying clinical phenotypes, and giving clues to underlying pathophysiological mechanisms in Parkinson’s disease and related disorders.

scholarly journals Evaluation of fecal microbiota transplantation in Parkinson's disease patients with constipation

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiao-yi Kuai ◽  
Xiao-han Yao ◽  
Li-juan Xu ◽  
Yu-qing Zhou ◽  
Li-ping Zhang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Neurodegenerative Disorder ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Motor Symptoms ◽  
Gastrointestinal Dysfunction ◽  
Before And After ◽  
Non Motor Symptoms

AbstractParkinson’s disease (PD) is a neurodegenerative disorder and 70–80% of PD patients suffer from gastrointestinal dysfunction such as constipation. We aimed to assess the efficacy and safety of fecal microbiota transplantation (FMT) for treating PD related to gastrointestinal dysfunction. We conducted a prospective, single- study. Eleven patients with PD received FMT. Fecal samples were collected before and after FMT and subjected to 16S ribosomal DNA (rDNA) gene sequencing. Hoehn-Yahr (H-Y) grade, Unified Parkinson's Disease Rating Scale (UPDRS) score, and the Non-Motion Symptom Questionnaire (NMSS) were used to assess improvements in motor and non-motor symptoms. PAC-QOL score and Wexner constipation score were used to assess the patient's constipation symptoms. All patients were tested by the small intestine breath hydrogen test, performed before and after FMT. Community richness (chao) and microbial structure in before-FMT PD patients were significantly different from the after-FMT. We observed an increased abundance of Blautia and Prevotella in PD patients after FMT, while the abundance of Bacteroidetes decreased dramatically. After FMT, the H-Y grade, UPDRS, and NMSS of PD patients decreased significantly. Through the lactulose H2 breath test, the intestinal bacterial overgrowth (SIBO) in PD patients returned to normal. The PAC-QOL score and Wexner constipation score in after-FMT patients decreased significantly. Our study profiles specific characteristics and microbial dysbiosis in the gut of PD patients. FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms.

scholarly journals Alpha-Synuclein Induced Immune Cells Activation and Associated Therapy in Parkinson’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Ruichen Su ◽  
Tian Zhou
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Immune System ◽  
Immune Cells ◽  
Neurodegenerative Disorder ◽  
Alpha Synuclein ◽  
Autoimmune Response ◽  
T Helper ◽  
Helper Type

Parkinson’s disease (PD) is a neurodegenerative disorder closely related to immunity. An important aspect of the pathogenesis of PD is the interaction between α-synuclein and a series of immune cells. Studies have shown that accumulation of α-synuclein can induce an autoimmune response that accelerates the progression of PD. This study discusses the mechanisms underlying the interaction between α-synuclein and the immune system. During the development of PD, abnormally accumulated α-synuclein becomes an autoimmune antigen that binds to Toll-like receptors (TLRs) that activate microglia, which differentiate into the microglia type 1 (M1) subtype. The microglia activate intracellular inflammatory pathways, induce the release of proinflammatory cytokines, and promote the differentiation of cluster of differentiation 4 + (CD4 +) T cells into proinflammatory T helper type 1 (Th1) and T helper type 17 (Th17) subtypes. Given the important role of α-synuclein in the immune system of the patients with PD, identifying potential targets of immunotherapy related to α-synuclein is critical for slowing disease progression. An enhanced understanding of immune-associated mechanisms in PD can guide the development of associated therapeutic strategies in the future.

scholarly journals Swallowing dysfunctions in Parkinson’s disease patients: a novel challenge for the internist

2019 ◽  
Vol 13 (2) ◽  
pp. 91-94 ◽  
Author(s):  
Elena Barbagelata ◽  
Antonello Nicolini ◽  
Paola Tognetti
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Practice ◽  
Aspiration Pneumonia ◽  
Neurodegenerative Disorder ◽  
Movement Pattern ◽  
Morbidity And Mortality ◽  
Motor Symptoms ◽  
Common Causes ◽  
Non Motor Symptoms

Parkinson’s disease (PD) is a chronic neurodegenerative disorder with a typical movement pattern, as well as different, less studied non-motor symptoms such as dysphagia. Disease-related disorders in efficacy or safety in the process of swallowing usually lead to malnutrition, dehydration or pneumonia. Dysphagia and subsequent aspiration pneumonia are common causes of morbidity and mortality in those with PD. The aim of this review is to identify and evaluate the existing literature on swallowing disorders in PD and providing recommendations for clinical practice routine.

scholarly journals Alpha-Synuclein and LRRK2 in Synaptic Autophagy: Linking Early Dysfunction to Late-Stage Pathology in Parkinson’s Disease

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1115 ◽  
Author(s):  
Giulia Lamonaca ◽  
Mattia Volta
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Late Stage ◽  
Disease Onset ◽  
Disease Process ◽  
Alpha Synuclein ◽  
Synaptic Activity ◽  
Early Event ◽  
Cellular Targets ◽  
Disease Modifying

The lack of effective disease-modifying strategies is the major unmet clinical need in Parkinson’s disease. Several experimental approaches have attempted to validate cellular targets and processes. Of these, autophagy has received considerable attention in the last 20 years due to its involvement in the clearance of pathologic protein aggregates and maintenance of neuronal homeostasis. However, this strategy mainly addresses a very late stage of the disease, when neuropathology and neurodegeneration have likely “tipped over the edge” and disease modification is extremely difficult. Very recently, autophagy has been demonstrated to modulate synaptic activity, a process distinct from its catabolic function. Abnormalities in synaptic transmission are an early event in neurodegeneration with Leucine-Rich Repeat Kinase 2 (LRRK2) and alpha-synuclein strongly implicated. In this review, we analyzed these processes separately and then discussed the unification of these biomolecular fields with the aim of reconstructing a potential “molecular timeline” of disease onset and progression. We postulate that the elucidation of these pathogenic mechanisms will form a critical basis for the design of novel, effective disease-modifying therapies that could be applied early in the disease process.

Impulse-Control Disorders in Parkinson's Disease

CNS Spectrums ◽  
2008 ◽  
Vol 13 (8) ◽  
pp. 690-698 ◽  
Author(s):  
Joseph M. Ferrara ◽  
Mark Stacy
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Replacement Therapy ◽  
Impulse Control ◽  
Neurodegenerative Disorder ◽  
Psychosocial Impairment ◽  
Olfactory Loss ◽  
Dopamine Replacement Therapy ◽  
Compulsive Behaviors ◽  
Non Motor Symptoms

ABSTRACTParkinson's disease is a neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, and resting tremor. Increasingly, Parkinson's disease has been associated with a broad spectrum of non-motor symptoms, such as olfactory loss, sleep disorders, autonomic dysfunction, cognitive impairment, psychosis, depression, anxiety, and apathy. In addition, a minority of Parkinson's disease patients develop compulsive behaviors while receiving dopamine-replacement therapy, including medication hoarding, pathological gambling, binge eating, hyperlibidinous behavior, compulsive shopping, and punding. These behaviors may result in psychosocial impairment for patients and therapeutic challenges for clinicians. This article reviews the anatomic substrates, behavioral spectrum, associated factors, and potential treatments for dopamine-replacement therapy-related compulsions in Parkinson's disease.

scholarly journals Non–motor Symptoms in Parkinson’s Disease: It’s Relationship with Age of Onset, Duration and Stage of Disease and the Dose and Duration of Levodopa Usage

1970 ◽  
Vol 21 (1) ◽  
pp. 12-17
Author(s):  
M Ahmed Ali ◽  
Anisul Haque ◽  
AKM Anwarulla ◽  
Quamruddin Ahmad
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Psychiatric Symptoms ◽  
Disease Onset ◽  
Motor Symptoms ◽  
Autonomic Symptoms ◽  
Prolonged Duration ◽  
Relationship Of ◽  
The Relationship ◽  
Non Motor Symptoms

Parkinson's disease is a disease of motor manifestations but non-motor symptoms are also common in Parkinson's disease. Little emphasis is put on non-motor symptoms of PD and there is little data on the relationship of non-motor symptoms to different aspects of the patient and the disease. In this study the relationship of non-motor symptoms to age at onset, duration and stage of the disease, and dose and duration of levodopa use are studied.128 patients of PD were studied for non-motor symptoms. 111 patients had different types of sensory, autonomic or psychiatric symptoms. Sensory and autonomic symptoms were significantly more common in patients with early age of disease onset and more prolonged duration of the disease, but psychiatric symptoms had no relationship with these factors. In this study it was also found that the frequencies of non-motor symptoms were related to the stage of the disease, longer the duration of the disease more and more non-motor symptoms appear so that 100% patients in stage 5 of the disease had non-motor symptoms. Also sensory and autonomic symptoms were significantly more common in patients with longer duration and higher dose of levodopa use but psychiatric symptoms were significantly commoner in patients with prolonged duration of levodopa use but not to dose of levodopa used.   doi: 10.3329/taj.v21i1.3211 TAJ 2008; 21(1): 12-17

scholarly journals Dynamic changes in the CD163+ and CCR2+ peripheral monocytes during Parkinson’s disease

2021 ◽  
Author(s):  
Sara Konstantin Nissen ◽  
Kristine Farmen ◽  
Mikkel Carstensen ◽  
Claudia Schulte ◽  
David Goldeck ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dendritic Cells ◽  
Alpha Synuclein ◽  
Mononuclear Phagocytes ◽  
Motor Symptoms ◽  
Hla Dr ◽  
Non Motor Symptoms ◽  
The Brain ◽  
Classical Monocytes

AbstractBackgroundAlpha-synuclein aggregates and accumulation are associated with immune activation and neurodegeneration in Parkinson’s disease. The immune activation is not only dependent on the brain-resident microglial cells but also involves peripheral immune cells, such as mononuclear phagocytes including monocytes and dendritic cells, found in the blood as well as infiltrated into the brain. Understanding the involvement of the peripheral immune component in Parkinson’s disease is essential for the development of immunomodulatory treatment, which might modify disease progression. We aimed to study the profile of circulating mononuclear phagocytes in early- and late-stage Parkinson’s disease by analyzing surface-expressed molecules related to phagocytosis, alpha-synuclein sensing, and tissue-migration.MethodsMulti-color flow cytometry on peripheral mononuclear cells from cross-sectional samples of 80 gender-balance individuals with early- and late-stage sporadic Parkinson’s disease, and 29 controls, as well as longitudinal samples from seven patients and one control. Cells were delineated into natural killer cells, monocyte subtypes, and dendritic cells with cell frequencies and surface marker expressions compared between patients and controls, and correlated with standardized clinical motor and non-motor scores.ResultsOverall, we found elevated frequencies and surface levels of markers related to migration (CCR2, CD11b) and phagocytosis (CD163) particularly on the elevated classical and intermediate monocytes in patients with Parkinson’s disease for less than five years. This corresponded to a decrease of non-classical monocytes and dendritic cells. We observed an increased HLA-DR expression late in disease and sexual-dimorphism with TLR-4 expression decreased in women with PD but not in males. The disease-associated immune changes on TLR4, CCR2, and CD11b were correlated with non-motor symptoms such as olfaction or cognition. While many alterations were normalized at late disease stage, other changes remained, such as the increased HLA-DR and CD163 expressions.ConclusionsOur data highlight a role for peripheral CD163+ and migration-competent classical monocytes in Parkinson’s disease. The study further suggests that the peripheral immune system is dynamically altered in Parkinson’s disease stages and directly related to both non-motor symptoms and the sex-bias of the disease.

scholarly journals Transgenic mice expressing human alpha-synuclein in noradrenergic neurons develop locus coeruleus pathology and non-motor features of Parkinson’s disease

2019 ◽  
Author(s):  
LM Butkovich ◽  
MC Houser ◽  
T Chalermpalanupap ◽  
KA Porter-Stransky ◽  
AF Iannitelli ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transgenic Mice ◽  
Locus Coeruleus ◽  
Transgenic Mouse ◽  
Alpha Synuclein ◽  
Striatal Dopamine ◽  
Motor Symptoms ◽  
Age Dependent ◽  
Non Motor Symptoms

AbstractDegeneration of locus coeruleus (LC) neurons and dysregulation of noradrenergic signaling are ubiquitous features of Parkinson’s disease (PD). The LC is among the first brain regions affected by α-synuclein (asyn) pathology, yet how asyn affects these neurons remains unclear. LC-derived norepinephrine (NE) can stimulate neuroprotective mechanisms and modulate immune cells, while dysregulation of NE neurotransmission may exacerbate disease progression, particularly non-motor symptoms, and contribute to the chronic neuroinflammation associated with PD pathology. Although transgenic mice overexpressing asyn have previously been developed, transgene expression is usually driven by pan-neuronal promoters and thus has not been selectively targeted to LC neurons. Here we report a novel transgenic mouse expressing human wild-type asyn under control of the noradrenergic-specific dopamine β-hydroxylase promoter. These mice developed oligomeric and conformation-specific asyn in LC neurons, alterations in hippocampal and LC microglial abundance, upregulated GFAP expression, degeneration of LC fibers, decreased striatal dopamine (DA) metabolism, and age-dependent behaviors reminiscent of non-motor symptoms of PD that were rescued by adrenergic receptor antagonists. These mice provide novel insights into how asyn pathology affects LC neurons and how central noradrenergic dysfunction may contribute to early PD pathophysiology.Significance statementα-synuclein (asyn) pathology and loss of neurons in the locus coeruleus (LC) are two of the most ubiquitous neuropathologic features of Parkinson’s disease (PD). Dysregulated NE neurotransmission is associated with the non-motor symptoms of PD including sleep disturbances, emotional changes such as anxiety and depression, and cognitive decline. Importantly, loss of central NE may contribute to the chronic inflammation in, and progression of, PD. We have generated a novel transgenic mouse expressing human asyn in LC neurons to investigate how increased asyn expression affects the function of the central noradrenergic transmission and associated behaviors. We report cytotoxic effects of oligomeric and conformation-specific asyn, astrogliosis, LC fiber degeneration, disruptions in striatal dopamine metabolism, and age-dependent alterations in non-motor behaviors without inclusions.

scholarly journals A clinical-anatomical signature of Parkinson’s Disease identified with partial least squares and magnetic resonance imaging

2017 ◽  
Author(s):  
Yashar Zeighami ◽  
Seyed-Mohammad Fereshtehnejad ◽  
Mahsa Dadar ◽  
D. Louis Collins ◽  
Ronald B. Postuma ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Least Squares ◽  
Partial Least Squares ◽  
Large Scale ◽  
De Novo ◽  
Neurodegenerative Disorder ◽  
Clinical Manifestations ◽  
Motor Symptoms ◽  
Non Motor Symptoms

AbstractParkinson’s disease (PD) is a neurodegenerative disorder characterized by a wide array of motor and non-motor symptoms. It remains unclear whether neurodegeneration in discrete loci gives rise to discrete symptoms, or whether network-wide atrophy gives rise to the unique behavioural and clinical profile associated with PD. Here we apply a data-driven strategy to isolate large-scale, multivariate associations between distributed atrophy patterns and clinical phenotypes in PD. In a sample of N = 229 de novo PD patients, we estimate disease-related atrophy using deformation based morphometry (DBM) of T1 weighted MR images. Using partial least squares (PLS), we identify a network of subcortical and cortical regions whose collective atrophy is associated with a clinical phenotype encompassing motor and non-motor features. Despite the relatively early stage of the disease in the sample, the atrophy pattern encompassed lower brainstem, substantia nigra, basal ganglia and cortical areas, consistent with the Braak hypothesis. In addition, individual variation in this putative atrophy network predicted longitudinal clinical progression in both motor and non-motor symptoms. Altogether, these results demonstrate a pleiotropic mapping between neurodegeneration and the clinical manifestations of PD, and that this mapping can be detected even in de novo patients.

scholarly journals Modelling Non-motor Symptoms of Parkinson’s Disease: AAV Mediated Overexpression of Alpha-synuclein in Rat Hippocampus and Basal Ganglia

2020 ◽  
Vol 26 (4) ◽  
pp. 322-329
Author(s):  
Sevgi Uğur Mutluay ◽  
Elif Çınar ◽  
Gül Yalçın Çakmaklı ◽  
Ayşe Ulusoy ◽  
Bülent Elibol ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Alpha Synuclein ◽  
Rat Hippocampus ◽  
Motor Symptoms ◽  
Non Motor Symptoms
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