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Neurochemical Research Oct 2023Parkinson's disease is a neurodegenerative disease affecting mainly the elderly population. It is characterized by the loss of dopaminergic neurons of the substantia... (Review)
Review
Parkinson's disease is a neurodegenerative disease affecting mainly the elderly population. It is characterized by the loss of dopaminergic neurons of the substantia nigra pars compacta region. Parkinson's disease patients exhibit motor symptoms like tremors, rigidity, bradykinesia/hypokinesia, and non-motor symptoms like depression, cognitive decline, delusion, and pain. Major pathophysiological factors which contribute to neuron loss include excess/misfolded alpha-synuclein aggregates, microglial cell-mediated neuroinflammation, excitotoxicity, oxidative stress, and defective mitochondrial function. Sigma-1 receptors are molecular chaperones located at mitochondria-associated ER membrane. Their activation (by endogenous ligands or agonists) has shown neuroprotective and neurorestorative effects in various diseases. This review discusses the roles of activated Sig-1 receptors in modulating various pathophysiological features of Parkinson's disease like alpha-synuclein aggregates, neuroinflammation, excitotoxicity, and oxidative stress.
Topics: Aged; Humans; Parkinson Disease; alpha-Synuclein; Neurodegenerative Diseases; Neuroinflammatory Diseases; Dopaminergic Neurons; Substantia Nigra; Sigma-1 Receptor
PubMed: 37259012
DOI: 10.1007/s11064-023-03960-6 -
Brain : a Journal of Neurology Mar 2024Dopaminergic dysfunction in the basal ganglia, particularly in the posterior putamen, is often viewed as the primary pathological mechanism behind motor slowing (i.e....
Dopaminergic dysfunction in the basal ganglia, particularly in the posterior putamen, is often viewed as the primary pathological mechanism behind motor slowing (i.e. bradykinesia) in Parkinson's disease. However, striatal dopamine loss fails to account for interindividual differences in motor phenotype and rate of decline, implying that the expression of motor symptoms depends on additional mechanisms, some of which may be compensatory in nature. Building on observations of increased motor-related activity in the parieto-premotor cortex of Parkinson patients, we tested the hypothesis that interindividual differences in clinical severity are determined by compensatory cortical mechanisms and not just by basal ganglia dysfunction. Using functional MRI, we measured variability in motor- and selection-related brain activity during a visuomotor task in 353 patients with Parkinson's disease (≤5 years disease duration) and 60 healthy controls. In this task, we manipulated action selection demand by varying the number of possible actions that individuals could choose from. Clinical variability was characterized in two ways. First, patients were categorized into three previously validated, discrete clinical subtypes that are hypothesized to reflect distinct routes of α-synuclein propagation: diffuse-malignant (n = 42), intermediate (n = 128) or mild motor-predominant (n = 150). Second, we used the scores of bradykinesia severity and cognitive performance across the entire sample as continuous measures. Patients showed motor slowing (longer response times) and reduced motor-related activity in the basal ganglia compared with controls. However, basal ganglia activity did not differ between clinical subtypes and was not associated with clinical scores. This indicates a limited role for striatal dysfunction in shaping interindividual differences in clinical severity. Consistent with our hypothesis, we observed enhanced action selection-related activity in the parieto-premotor cortex of patients with a mild-motor predominant subtype, both compared to patients with a diffuse-malignant subtype and controls. Furthermore, increased parieto-premotor activity was related to lower bradykinesia severity and better cognitive performance, which points to a compensatory role. We conclude that parieto-premotor compensation, rather than basal ganglia dysfunction, shapes interindividual variability in symptom severity in Parkinson's disease. Future interventions may focus on maintaining and enhancing compensatory cortical mechanisms, rather than only attempting to normalize basal ganglia dysfunction.
Topics: Humans; Parkinson Disease; Hypokinesia; Basal Ganglia; Corpus Striatum; Dopamine; Putamen
PubMed: 37757883
DOI: 10.1093/brain/awad325 -
Ageing Research Reviews Jan 2024Cardinal motor symptoms in Parkinson's disease (PD) include bradykinesia, rest tremor and/or rigidity. This symptomatology can additionally encompass abnormal gait,... (Review)
Review
Cardinal motor symptoms in Parkinson's disease (PD) include bradykinesia, rest tremor and/or rigidity. This symptomatology can additionally encompass abnormal gait, balance and postural patterns at advanced stages of the disease. Besides pharmacological and surgical therapies, physical exercise represents an important strategy for the management of these advanced impairments. Traditionally, diagnosis and classification of such abnormalities have relied on partially subjective evaluations performed by neurologists during short and temporally scattered hospital appointments. Emerging sports medical methods, including wearable sensor-based movement assessment and computational-statistical analysis, are paving the way for more objective and systematic diagnoses in everyday life conditions. These approaches hold promise to facilitate customizing clinical trials to specific PD groups, as well as personalizing neuromodulation therapies and exercise prescriptions for each individual, remotely and regularly, according to disease progression or specific motor symptoms. We aim to summarize exercise benefits for PD with a specific emphasis on gait and balance deficits, and to provide an overview of recent advances in movement analysis approaches, notably from the sports science community, with value for diagnosis and prognosis. Although such techniques are becoming increasingly available, their standardization and optimization for clinical purposes is critically missing, especially in their translation to complex neurodegenerative disorders such as PD. We highlight the importance of integrating state-of-the-art gait and movement analysis approaches, in combination with other motor, electrophysiological or neural biomarkers, to improve the understanding of the diversity of PD phenotypes, their response to therapies and the dynamics of their disease progression.
Topics: Humans; Parkinson Disease; Exercise Therapy; Gait; Disease Progression; Exercise
PubMed: 38036102
DOI: 10.1016/j.arr.2023.102147 -
Neural Regeneration Research Jul 2023Parkinson's disease is the most common movement disorder, affecting about 1% of the population over the age of 60 years. Parkinson's disease is characterized clinically... (Review)
Review
Parkinson's disease is the most common movement disorder, affecting about 1% of the population over the age of 60 years. Parkinson's disease is characterized clinically by resting tremor, bradykinesia, rigidity and postural instability, as a result of the progressive loss of nigrostriatal dopaminergic neurons. In addition to this neuronal cell loss, Parkinson's disease is characterized by the accumulation of intracellular protein aggregates, Lewy bodies and Lewy neurites, composed primarily of the protein α-synuclein. Although it was first described almost 200 years ago, there are no disease-modifying drugs to treat patients with Parkinson's disease. In addition to conventional therapies, non-pharmacological treatment strategies are under investigation in patients and animal models of neurodegenerative disorders. Among such strategies, environmental enrichment, comprising physical exercise, cognitive stimulus, and social interactions, has been assessed in preclinical models of Parkinson's disease. Environmental enrichment can cause structural and functional changes in the brain and promote neurogenesis and dendritic growth by modifying gene expression, enhancing the expression of neurotrophic factors and modulating neurotransmission. In this review article, we focus on the current knowledge about the molecular mechanisms underlying environmental enrichment neuroprotection in Parkinson's disease, highlighting its influence on the dopaminergic, cholinergic, glutamatergic and GABAergic systems, as well as the involvement of neurotrophic factors. We describe experimental pre-clinical data showing how environmental enrichment can act as a modulator in a neurochemical and behavioral context in different animal models of Parkinson's disease, highlighting the potential of environmental enrichment as an additional strategy in the management and prevention of this complex disease.
PubMed: 36571341
DOI: 10.4103/1673-5374.360264 -
Journal of Medical Internet Research Aug 2023The prevalence of Parkinson disease (PD) is becoming an increasing concern owing to the aging population in the United Kingdom. Wearable devices have the potential to... (Review)
Review
BACKGROUND
The prevalence of Parkinson disease (PD) is becoming an increasing concern owing to the aging population in the United Kingdom. Wearable devices have the potential to improve the clinical care of patients with PD while reducing health care costs. Consequently, exploring the features of these wearable devices is important to identify the limitations and further areas of investigation of how wearable devices are currently used in clinical care in the United Kingdom.
OBJECTIVE
In this scoping review, we aimed to explore the features of wearable devices used for PD in hospitals in the United Kingdom.
METHODS
A scoping review of the current research was undertaken and reported according to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. The literature search was undertaken on June 6, 2022, and publications were obtained from MEDLINE or PubMed, Embase, and the Cochrane Library. Eligible publications were initially screened by their titles and abstracts. Publications that passed the initial screening underwent a full review. The study characteristics were extracted from the final publications, and the evidence was synthesized using a narrative approach. Any queries were reviewed by the first and second authors.
RESULTS
Of the 4543 publications identified, 39 (0.86%) publications underwent a full review, and 20 (0.44%) publications were included in the scoping review. Most studies (11/20, 55%) were conducted at the Newcastle upon Tyne Hospitals NHS Foundation Trust, with sample sizes ranging from 10 to 418. Most study participants were male individuals with a mean age ranging from 57.7 to 78.0 years. The AX3 was the most popular device brand used, and it was commercially manufactured by Axivity. Common wearable device types included body-worn sensors, inertial measurement units, and smartwatches that used accelerometers and gyroscopes to measure the clinical features of PD. Most wearable device primary measures involved the measured gait, bradykinesia, and dyskinesia. The most common wearable device placements were the lumbar region, head, and wrist. Furthermore, 65% (13/20) of the studies used artificial intelligence or machine learning to support PD data analysis.
CONCLUSIONS
This study demonstrated that wearable devices could help provide a more detailed analysis of PD symptoms during the assessment phase and personalize treatment. Using machine learning, wearable devices could differentiate PD from other neurodegenerative diseases. The identified evidence gaps include the lack of analysis of wearable device cybersecurity and data management. The lack of cost-effectiveness analysis and large-scale participation in studies resulted in uncertainty regarding the feasibility of the widespread use of wearable devices. The uncertainty around the identified research gaps was further exacerbated by the lack of medical regulation of wearable devices for PD, particularly in the United Kingdom where regulations were changing due to the political landscape.
Topics: Humans; Male; Aged; Middle Aged; Female; Parkinson Disease; Artificial Intelligence; Aging; Commerce; Hospitals
PubMed: 37594791
DOI: 10.2196/42950 -
Cureus Jan 2024Parkinson's disease (PD) is a common, prevalent neurodegenerative disease. It is mainly characterized by motor symptoms such as rigidity, tremors, and bradykinesia, but... (Review)
Review
Parkinson's disease (PD) is a common, prevalent neurodegenerative disease. It is mainly characterized by motor symptoms such as rigidity, tremors, and bradykinesia, but it can also manifest with non-motor symptoms, of which depression is the most frequent. The latter can impair the quality of life, yet it gets overlooked and goes untreated because of the significant overlap in their clinical features, hence making the diagnosis difficult. Furthermore, there is limited data on the availability of appropriate criteria for making the diagnosis of depression in PD patients, as it can occur with varying expressions throughout the course of PD or it can also precede it. This review article has included a brief discussion on the diagnosis of depression in PD patients and their overlapped clinical manifestations. Understanding the mechanisms underlying the disease processes of PD and depression and the pathways interconnecting them gives better knowledge on devising treatment options for the patients. Only studies from Pubmed were included and all other databases were excluded. Studies from the last 50 years were included. Suitable references included in these studies were also extracted. Thus, depression in PD and PD in depression, along with their pharmacological and non-pharmacological treatment options, have been discussed.
PubMed: 38380213
DOI: 10.7759/cureus.52663 -
International Journal of Molecular... Dec 2023Parkinson's disease is a neurodegenerative condition characterized by motor dysfunction resulting from the degeneration of dopamine-producing neurons in the midbrain.... (Review)
Review
Parkinson's disease is a neurodegenerative condition characterized by motor dysfunction resulting from the degeneration of dopamine-producing neurons in the midbrain. This dopamine deficiency gives rise to a spectrum of movement-related symptoms, including tremors, rigidity, and bradykinesia. While the precise etiology of Parkinson's disease remains elusive, genetic mutations, protein aggregation, inflammatory processes, and oxidative stress are believed to contribute to its development. In this context, fatty acid-binding proteins (FABPs) in the central nervous system, FABP3, FABP5, and FABP7, impact α-synuclein aggregation, neurotoxicity, and neuroinflammation. These FABPs accumulate in mitochondria during neurodegeneration, disrupting their membrane potential and homeostasis. In particular, FABP3, abundant in nigrostriatal dopaminergic neurons, is responsible for α-synuclein propagation into neurons and intracellular accumulation, affecting the loss of mesencephalic tyrosine hydroxylase protein, a rate-limiting enzyme of dopamine biosynthesis. This review summarizes the characteristics of FABP family proteins and delves into the pathogenic significance of FABPs in the pathogenesis of Parkinson's disease. Furthermore, it examines potential novel therapeutic targets and early diagnostic biomarkers for Parkinson's disease and related neurodegenerative disorders.
Topics: Humans; Parkinson Disease; alpha-Synuclein; Dopamine; Fatty Acid-Binding Proteins; Neurodegenerative Diseases; Dopaminergic Neurons
PubMed: 38069360
DOI: 10.3390/ijms242317037 -
Journal of Integrative Neuroscience Jan 2024Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor symptoms such as tremors, rigidity, and bradykinesia. While the diagnosis of PD primarily... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor symptoms such as tremors, rigidity, and bradykinesia. While the diagnosis of PD primarily relies on clinical assessments and neurological examination, there has been growing interest in exploring non-invasive imaging techniques to aid in early detection and monitoring of the disease. In recent years, retinal imaging has emerged as a promising tool for studying PD due to the close anatomical and functional similarities between the retina and the brain. Retinal imaging methods, such as spectral domain optical coherence tomography and optical coherence tomography angiography, enable non-intrusive visualization and measurement of retinal structures and blood vessels. These techniques hold the promise of capturing alterations in retinal structure and function that could potentially mirror the underlying pathological mechanisms in PD. This review article aims to provide an overview of the current understanding of retinal changes in PD and the potential utility of retinal imaging as a diagnostic and monitoring tool.
Topics: Humans; Parkinson Disease; Retina; Tomography, Optical Coherence; Brain
PubMed: 38287853
DOI: 10.31083/j.jin2301023