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Biomedicine & Pharmacotherapy =... Dec 2023Degenerative musculoskeletal disorders are a group of age-related diseases of the locomotive system that severely affects the patient's ability to work and cause adverse... (Review)
Review
Degenerative musculoskeletal disorders are a group of age-related diseases of the locomotive system that severely affects the patient's ability to work and cause adverse sequalae such as fractures and even death. The incidence and prevalence of degenerative musculoskeletal disorders is rising owing to the aging of the world's population. The Notch signaling pathway, which is expressed in almost all organ systems, extensively regulates cell proliferation and differentiation as well as cellular fate. Notch signaling shows increased activity in degenerative musculoskeletal disorders and retards the progression of degeneration to some extent. The review focuses on four major degenerative musculoskeletal disorders (osteoarthritis, intervertebral disc degeneration, osteoporosis, and sarcopenia) and summarizes the pathophysiological functions of Notch signaling in these disorders, especially its role in stem/progenitor cells in each disorder. Finally, a conclusion will be presented to explore the research and application of the perspectives on Notch signaling in degenerative musculoskeletal disorders.
Topics: Humans; Intervertebral Disc Degeneration; Signal Transduction; Osteoarthritis; Aging; Osteoporosis
PubMed: 37981460
DOI: 10.1016/j.biopha.2023.115884 -
Advances in Experimental Medicine and... 2022The cerebellum is involved in almost all cognitive functions related to music perception and music production. This has been shown by functional imaging and by similar...
The cerebellum is involved in almost all cognitive functions related to music perception and music production. This has been shown by functional imaging and by similar techniques. In addition, lesion studies (i.e. examining patients with cerebellar infarction or tumour) also give evidence of this involvement. Different parts of the cerebellum have been identified for different aspects of these processing tasks and their individual connections to the cerebral cortex as well as to the basal ganglia. It has been shown for example that cerebellar disorders impair music perception in particular in melody comparison and metrum tasks. First research approaches are trying to use the current knowledge on the role of the cerebellum in music perception for therapeutic processes in degenerative disorders such as Alzheimer's disease.
Topics: Basal Ganglia; Brain Ischemia; Cerebellum; Cognition; Humans; Music
PubMed: 35902473
DOI: 10.1007/978-3-030-99550-8_13 -
Neurological Sciences : Official... Mar 2022Efferocytosis has a critical role in maintaining tissues and organs' homeostasis by removing apoptotic cells. It is essential for human health, and disturbances in... (Review)
Review
Efferocytosis has a critical role in maintaining tissues and organs' homeostasis by removing apoptotic cells. It is essential for human health, and disturbances in efferocytosis may result indifferent illnesses. In case of inadequate clearance of the dead cells, the content in the cells would be released. In fact, it induces some damages to the tissue and leads to the prolonged inflammation, so unsuitable phagocytosis of the apoptotic cells is involved in occurrence as well as expansion of numerous human chronic inflammatory diseases. Studies have shown age dependence of the neuro-degenerative diseases, which are largely due to the neuro-inflammation and the loss of neurons and thus cause the brain's functional disorders. Efferocytosis is coupled to anti-inflammatory responses that contribute to the elimination of the dying neurons in neuro-degenerative diseases, so its disruption may make a risk factor in numerous human chronic inflammatory diseases such as multiple sclerosis, Alzheimer's disease, glioblastoma, and Rett syndrome. This study is a review of the efferocytosis molecular pathways and their role in neuro-degenerative diseases in order to discover a new treatment option to cure patients.
Topics: Apoptosis; Homeostasis; Humans; Inflammation; Macrophages; Phagocytosis
PubMed: 35059903
DOI: 10.1007/s10072-021-05835-6 -
Regenerative Therapy Dec 2020Osteoarthritis () is the most common chronic musculoskeletal disorder. It can affect any joint and is the most frequent single cause of disability in older adults. is a... (Review)
Review
Osteoarthritis () is the most common chronic musculoskeletal disorder. It can affect any joint and is the most frequent single cause of disability in older adults. is a progressive degenerative disease involving the entire joint structure in a vicious circle that includes the capsule-bursa tissue inflammation, synovial fluid modifications, cartilage breakdown and erosions, osteochondral inflammatory damage leading to bone erosion and distortion. Research has identified the initial inflammatory-immunologic process that starts this vicious cycle leading to so-called Research has also identified the role played in the disease advancement by synoviocytes and , chondrocytes, extracellular matrix, local immune-inflammatory mediators and proteases. This article investigates the joint-resident that play an essential local homeostatic role and regulate cell turn over and tissue repair. Resident establish and maintain a local . The understanding of physiopathology clarifies the core mechanisms by which minimally invasive interventions might be able to halt and reverse the course of early stage . Interventions employing , and are considered in this article.
PubMed: 33426213
DOI: 10.1016/j.reth.2020.07.007 -
Handbook of Clinical Neurology 2021Degenerative dementias such as Alzheimer's disease and frontotemporal dementia result in distinct alterations in emotional processing, emotional experiences, and mood.... (Review)
Review
Degenerative dementias such as Alzheimer's disease and frontotemporal dementia result in distinct alterations in emotional processing, emotional experiences, and mood. The neuropathology of these dementias extends to structures involved in emotional processing, including the basolateral limbic network (orbitofrontal cortex, anterior temporal lobe, amygdala, and thalamus), the insula, and ventromedial frontal lobe. Depression is the most common emotion and mood disorder affecting patients with Alzheimer's disease. The onset of depression can be a prodromal sign of this dementia. Anxiety can also be present early in the course of Alzheimer's disease and especially among patients with early-onset forms of the disease. In contrast, patients with behavioral variant frontotemporal dementia demonstrate hypoemotionality, deficits in the recognition of emotion, and decreased psychophysiological reactivity to emotional stimuli. They typically have a disproportionate impairment in emotional and cognitive empathy. One other unique feature of behavioral variant frontotemporal dementia is the frequent occurrence of bipolar disorder. The management strategies for these alterations of emotion and mood in degenerative dementias primarily involve the judicious use of the psychiatric armamentarium of medications.
Topics: Alzheimer Disease; Emotions; Empathy; Frontotemporal Dementia; Humans; Magnetic Resonance Imaging; Mood Disorders; Neuropsychological Tests
PubMed: 34389121
DOI: 10.1016/B978-0-12-822290-4.00012-8 -
Nature Reviews. Neurology Feb 2022Intellectual disability and autism spectrum disorder (ASD) are common, and genetic testing is increasingly performed in individuals with these diagnoses to inform... (Review)
Review
Intellectual disability and autism spectrum disorder (ASD) are common, and genetic testing is increasingly performed in individuals with these diagnoses to inform prognosis, refine management and provide information about recurrence risk in the family. For neurogenetic conditions associated with intellectual disability and ASD, data on natural history in adults are scarce; however, as older adults with these disorders are identified, it is becoming clear that some conditions are associated with both neurodevelopmental problems and neurodegeneration. Moreover, emerging evidence indicates that some neurogenetic conditions associated primarily with neurodegeneration also affect neurodevelopment. In this Perspective, we discuss examples of diseases that have developmental and degenerative overlap. We propose that neurogenetic disorders should be studied continually across the lifespan to understand the roles of the affected genes in brain development and maintenance, and to inform strategies for treatment.
Topics: Aged; Autism Spectrum Disorder; Genetic Testing; Humans; Intellectual Disability; Longevity
PubMed: 34987232
DOI: 10.1038/s41582-021-00595-5 -
Frontiers in Molecular Neuroscience 2023Alzheimer's disease (AD) is a central nervous system (CNS) degenerative disorder, is caused by various factors including β-amyloid toxicity, hyperphosphorylation of tau... (Review)
Review
Alzheimer's disease (AD) is a central nervous system (CNS) degenerative disorder, is caused by various factors including β-amyloid toxicity, hyperphosphorylation of tau protein, oxidative stress, and others. The dysfunction of microglia has been associated with the onset and advancement of different neurodevelopmental and neurodegenerative disorders, such as AD. The gut of mammals harbors a vast and complex population of microorganisms, commonly referred to as the microbiota. There's a growing recognition that these gut microbes are intrinsically intertwined with mammalian physiology. Through the circulation of metabolites, they establish metabolic symbiosis, enhance immune function, and establish communication with different remote cells, including those in the brain. The gut microbiome plays a crucial part in influencing the development and performance of microglia, as indicated by recent preclinical studies. Dysbiosis of the intestinal flora leads to alterations in the microglia transcriptome that regulate the interconversion of microglia subtypes. This conversation explores recent research that clarifies how gut bacteria, their byproducts, and harmful elements affect the activation and characteristics of microglia. This understanding opens doors to innovative microbial-based therapeutic strategies for early identification and treatment goals in AD.
PubMed: 38098943
DOI: 10.3389/fnmol.2023.1295916 -
Brain Sciences Feb 2022We previously suggested that stochastic processes are fundamental in the development of sporadic adult onset neurodegenerative disorders. In this study, we develop a...
We previously suggested that stochastic processes are fundamental in the development of sporadic adult onset neurodegenerative disorders. In this study, we develop a theoretical framework to explain stochastic processes at the protein, DNA and RNA levels. We propose that probability determines random sequencing changes, some of which favor neurodegeneration in particular anatomical spaces, and that more than one protein may be affected simultaneously. The stochastic protein changes happen in three-dimensional space and can be considered to be vectors in a space-time continuum, their trajectories and kinetics modified by physiological variables in the manifold of intra- and extra-cellular space. The molecular velocity of these degenerative proteins must obey the second law of thermodynamics, in which entropy is the driver of the inexorable progression of neurodegeneration in the context of the N-body problem of interacting proteins, time-space manifold of protein-protein interactions in phase space, and compounded by the intrinsic disorder of protein-protein networks. This model helps to elucidate the existence of multiple misfolded proteinopathies in adult sporadic neurodegenerative disorders.
PubMed: 35203989
DOI: 10.3390/brainsci12020226 -
JPRAS Open Mar 2022Macrodactyly is a rare congenital disorder of overgrowth affecting the digits of the upper or lower extremity. Mostly, patients are surgically treated during childhood...
BACKGROUND
Macrodactyly is a rare congenital disorder of overgrowth affecting the digits of the upper or lower extremity. Mostly, patients are surgically treated during childhood to reduce the digit or to stop growth. There are no standardized guidelines for the treatment and follow-up of macrodactyly. Consequently, follow-up may not be regularly scheduled into adulthood.
METHODS
A retrospective, descriptive analysis of patients with the long-term progression of macrodactyly who presented at our tertiary referral hospital between July 2018 and March 2020 was performed. All patients from our local macrodactyly database were screened for progression of macrodactyly since adulthood; this resulted in four patients. The aim of these case series is to highlight the clinical features and disease course at long-term follow-up.
RESULTS
All patients were surgically treated during childhood and showed progression of tissue overgrowth during adult life. All patients developed severe secondary degenerative bone changes in macrodactyly affected digits, such as ankyloses of joints, new bone formation, and bony spurs. Subsequently, tissue overgrowth and degenerative bone changes led to functional problems.
CONCLUSION
Patients with macrodactyly may experience growth during adult life, which may progress to deforming changes. Consequently, patients should be informed about the possible growth, and the progressive growth should be monitored.
PubMed: 34869816
DOI: 10.1016/j.jpra.2021.10.004 -
Journal of Neural Transmission (Vienna,... Apr 2023Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by early postural instability and falls, oculomotor dysfunction (vertical supranuclear... (Review)
Review
Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by early postural instability and falls, oculomotor dysfunction (vertical supranuclear gaze palsy), parkinsonism with poor response to levodopa, pseudobulbar palsy, and cognitive impairment. This four-repeat tauopathy is morphologically featured by accumulation of tau protein in neurons and glia causing neuronal loss and gliosis in the extrapyramidal system associated with cortical atrophy and white matter lesions. Cognitive impairment being frequent in PSP and more severe than in multiple system atrophy and Parkinson disease, is dominated by executive dysfunction, with milder difficulties in memory, and visuo-spatial and naming dysfunctions. Showing longitudinal decline, it has been related to a variety of pathogenic mechanisms associated with the underlying neurodegenerative process, such as involvement of cholinergic and muscarinergic dysfunctions, and striking tau pathology in frontal and temporal cortical regions associated with reduced synaptic density. Altered striatofrontal, fronto-cerebellar, parahippocampal, and multiple subcortical structures, as well as widespread white matter lesions causing extensive connectivity disruptions in cortico-subcortical and cortico-brainstem connections, support the concept that PSP is a brain network disruption disorder. The pathophysiology and pathogenesis of cognitive impairment in PSP, as in other degenerative movement disorders, are complex and deserve further elucidation as a basis for adequate treatment to improve the quality of life of patients with this fatal disease.
Topics: Humans; Supranuclear Palsy, Progressive; Quality of Life; Parkinsonian Disorders; Parkinson Disease; Neurodegenerative Diseases; Cognitive Dysfunction
PubMed: 36862189
DOI: 10.1007/s00702-023-02613-w