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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 -
Neurology India 2021Normal-pressure hydrocephalus (NPH) presents with the triad of gait difficulty, urinary incontinence, and cognitive decline. However, the definitive diagnosis and... (Review)
Review
BACKGROUND
Normal-pressure hydrocephalus (NPH) presents with the triad of gait difficulty, urinary incontinence, and cognitive decline. However, the definitive diagnosis and treatment may be challenging at times due to secondary causes of NPH (sNPH) versus idiopathic NPH (iNPH), co-existing other degenerative, vascular, and metabolic causes of similar clinical presentations.
OBJECTIVE
The objective of this narrative review is to outline the approach to patient evaluation and decision-making in cases where there is clinical suspicion of iNPH.
METHODS
This review article intends to provide a practical approach to the patients with a suspected diagnosis of iNPH.
RESULTS
The cardinal clinical features with a guide from investigations like magnetic resonance imaging (MRI) brain and cerebrospinal fluid (CSF) analysis, and CSF tap assessment have been outlined. The interpretation of conflicting MRI brain findings or CSF analysis may need resolution by further tests. The decision algorithm following the examination and investigations has been included to address the dilemma in the case of a non-supportive MRI and/or CSF tap test.
CONCLUSION
iNPH is a treatable cause of the cognitive decline and gait disorder. While neurodegenerative causes may accompany iNPH, any patient with improvement after CSF drainage deserves therapeutic intervention.
Topics: Humans; Hydrocephalus, Normal Pressure; Magnetic Resonance Imaging; Movement Disorders; Neuroimaging
PubMed: 35102996
DOI: 10.4103/0028-3886.332267 -
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 -
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 -
Frontiers in Toxicology 2022Neurodegeneration leads to the loss of structural and functioning components of neurons over time. Various studies have related neurodegeneration to a number of... (Review)
Review
Neurodegeneration leads to the loss of structural and functioning components of neurons over time. Various studies have related neurodegeneration to a number of degenerative disorders. Neurological repercussions of neurodegeneration can have severe impacts on the physical and mental health of patients. In the recent past, various neurodegenerative ailments such as Alzheimer's and Parkinson's illnesses have received global consideration owing to their global occurrence. Environmental attributes have been regarded as the main contributors to neural dysfunction-related disorders. The majority of neurological diseases are mainly related to prenatal and postnatal exposure to industrially produced environmental toxins. Some neurotoxic metals, like lead (Pb), aluminium (Al), Mercury (Hg), manganese (Mn), cadmium (Cd), and arsenic (As), and also pesticides and metal-based nanoparticles, have been implicated in Parkinson's and Alzheimer's disease. The contaminants are known for their ability to produce senile or amyloid plaques and neurofibrillary tangles (NFTs), which are the key features of these neurological dysfunctions. Besides, solvent exposure is also a significant contributor to neurological diseases. This study recapitulates the role of environmental neurotoxins on neurodegeneration with special emphasis on major neurodegenerative disorders such as Alzheimer's and Parkinson's disease.
PubMed: 35647576
DOI: 10.3389/ftox.2022.837579 -
Movement Disorders : Official Journal... Jan 2021Parkinson's disease is a progressive and debilitating disorder that has so far eluded attempts to develop disease-modifying treatment. Both epidemiological and genetic... (Review)
Review
Parkinson's disease is a progressive and debilitating disorder that has so far eluded attempts to develop disease-modifying treatment. Both epidemiological and genetic studies support a role of neuroinflammation in the pathophysiology of Parkinson's disease. Postmortem studies and experimental analyses suggest the involvement of both innate and adaptive immunity in the degenerative process. There is also some circumstantial evidence for effects of immune therapies on the disease. In the present article, we review 10 unanswered questions related to neuroinflammatory processes in Parkinson's disease with the goal of stimulating research in the field and accelerating the clinical development of neuroprotective therapies based on anti-inflammatory strategies. © 2020 International Parkinson and Movement Disorder Society.
Topics: Humans; Parkinson Disease; alpha-Synuclein
PubMed: 32357266
DOI: 10.1002/mds.28075 -
Seminars in Neurology Feb 2023A variety of etiologies can cause cerebellar dysfunction, leading to ataxia symptoms. Therefore, the accurate diagnosis of the cause for cerebellar ataxia can be...
A variety of etiologies can cause cerebellar dysfunction, leading to ataxia symptoms. Therefore, the accurate diagnosis of the cause for cerebellar ataxia can be challenging. A step-wise investigation will reveal underlying causes, including nutritional, toxin, immune-mediated, genetic, and degenerative disorders. Recent advances in genetics have identified new genes for both autosomal dominant and autosomal recessive ataxias, and new therapies are on the horizon for targeting specific biological pathways. New diagnostic criteria for degenerative ataxias have been proposed, specifically for multiple system atrophy, which will have a broad impact on the future clinical research in ataxia. In this article, we aim to provide a review focus on symptoms, laboratory testing, neuroimaging, and genetic testing for the diagnosis of cerebellar ataxia causes, with a special emphasis on recent advances. Strategies for the management of cerebellar ataxia is also discussed.
Topics: Humans; Cerebellar Ataxia; Ataxia; Genetic Testing; Multiple System Atrophy; Neuroimaging
PubMed: 36828010
DOI: 10.1055/s-0043-1763511