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World Journal of Orthopedics Jul 2019Inactivity contributes to chronic diseases, including diabetes, hypertension, cardiovascular disorders, and obesity. Sedentary habits can shorten life expectancy.... (Review)
Review
Inactivity contributes to chronic diseases, including diabetes, hypertension, cardiovascular disorders, and obesity. Sedentary habits can shorten life expectancy. Exercise has been widely proposed as a valuable approach to prevention. Regular physical activity, as part of one's daily routine, may help to manage pathological conditions. This editorial especially addresses osteoarthritis (OA), a degenerative disease of the articular cartilage, which is one of the most common causes of disability worldwide. Standard treatments for this illness include surgical procedures and pharmacological management; behavioural approaches are also strongly recommended. Physical exercise represents a practical strategy to preserve function, decrease pain and fatigue, and increase muscle strength and flexibility. We suggest that physical activity be considered as an established form of treatment, which means including exercise in standard therapeutic guidelines. A growing number of patients suffer from preventable chronic conditions that impose a heavy social and economic burden on the healthcare system. Preventive exercise training should be prescribed in the same way as pharmaceuticals.
PubMed: 31363456
DOI: 10.5312/wjo.v10.i7.262 -
International Journal of Molecular... May 2024Oxidative stress and inflammation are recognized as pivotal contributors and common features of several chronic degenerative diseases, including cancer, metabolic...
Oxidative stress and inflammation are recognized as pivotal contributors and common features of several chronic degenerative diseases, including cancer, metabolic syndrome, type 2 diabetes, cardiovascular diseases and neurodegenerative disorders, affecting a high percentage of the population [...].
Topics: Oxidative Stress; Humans; Inflammation; Neurodegenerative Diseases; Chronic Disease; Diabetes Mellitus, Type 2; Cardiovascular Diseases; Animals; Metabolic Syndrome
PubMed: 38732245
DOI: 10.3390/ijms25095026 -
Stem Cell Research & Therapy Dec 2021Optic neuritis (ON) is frequently encountered in multiple sclerosis, neuromyelitis optica spectrum disorder, anti-myelin oligodendrocyte glycoprotein associated disease,... (Review)
Review
BACKGROUND
Optic neuritis (ON) is frequently encountered in multiple sclerosis, neuromyelitis optica spectrum disorder, anti-myelin oligodendrocyte glycoprotein associated disease, and other systemic autoimmune disorders. The hallmarks are an abnormal optic nerve and inflammatory demyelination; episodes of optic neuritis tend to be recurrent, and particularly for neuromyelitis optica spectrum disorder, may result in permanent vision loss.
MAIN BODY
Mesenchymal stem cell (MSC) therapy is a promising approach that results in remyelination, neuroprotection of axons, and has demonstrated success in clinical studies in other neuro-degenerative diseases and in animal models of ON. However, cell transplantation has significant disadvantages and complications. Cell-free approaches utilizing extracellular vesicles (EVs) produced by MSCs exhibit anti-inflammatory and neuroprotective effects in multiple animal models of neuro-degenerative diseases and in rodent models of multiple sclerosis (MS). EVs have potential to be an effective cell-free therapy in optic neuritis because of their anti-inflammatory and remyelination stimulating properties, ability to cross the blood brain barrier, and ability to be safely administered without immunosuppression.
CONCLUSION
We review the potential application of MSC EVs as an emerging treatment strategy for optic neuritis by reviewing studies in multiple sclerosis and related disorders, and in neurodegeneration, and discuss the challenges and potential rewards of clinical translation of EVs including cell targeting, carrying of therapeutic microRNAs, and prolonging delivery for treatment of optic neuritis.
Topics: Animals; Extracellular Vesicles; Mesenchymal Stem Cells; Myelin-Oligodendrocyte Glycoprotein; Neuromyelitis Optica; Optic Neuritis
PubMed: 34863294
DOI: 10.1186/s13287-021-02645-7 -
Molecules (Basel, Switzerland) Mar 2024Alzheimer's disease (AD) is a complex degenerative disease of the central nervous system that is clinically characterized by a progressive decline in memory and... (Review)
Review
Alzheimer's disease (AD) is a complex degenerative disease of the central nervous system that is clinically characterized by a progressive decline in memory and cognitive function. The pathogenesis of AD is intricate and not yet fully understood. Neuroinflammation, particularly microglial activation-mediated neuroinflammation, is believed to play a crucial role in increasing the risk, triggering the onset, and hastening the progression of AD. Modulating microglial activation and regulating microglial energy metabolic disorder are seen as promising strategies to intervene in AD. The application of anti-inflammatory drugs and the targeting of microglia for the prevention and treatment of AD has emerged as a new area of research interest. This article provides a comprehensive review of the role of neuroinflammation of microglial regulation in the development of AD, exploring the connection between microglial energy metabolic disorder, neuroinflammation, and AD development. Additionally, the advancements in anti-inflammatory and microglia-regulating therapies for AD are discussed.
Topics: Humans; Alzheimer Disease; Microglia; Neuroinflammatory Diseases; Central Nervous System; Anti-Inflammatory Agents
PubMed: 38611758
DOI: 10.3390/molecules29071478 -
Cureus Sep 2023To diagnose and predict the possibility of Alzheimer's or a different kind of dementia, medical professionals employ tests that look at a patient's mental competence;... (Review)
Review
To diagnose and predict the possibility of Alzheimer's or a different kind of dementia, medical professionals employ tests that look at a patient's mental competence; however, such methods are impracticable. A reliable diagnosis at the start of treatment is essential for therapy. Except in situations with apparent genetic variations, most Alzheimer's patients lack a known etiology. Therefore, every Alzheimer's patient receives the same treatment plan, regardless of the etiology, which may or may not be successful in slowing or preventing the disease's progression. Tau pathology is further complicated by the amyloid buildup that arises from the cellular phase of Alzheimer's disease (AD). Alzheimer's is a degenerative, diverse, complicated, and incurable neurological disorder primarily affecting elderly individuals. The currently accepted drugs available for treating AD, which involve cholinesterase inhibitors and N-methyl-D-aspartate NMDA)-receptor antagonists only provide temporary relief from symptoms. The neurological disorder primarily affecting elderly individuals is degenerative, diverse, complicated, and incurable. Accurate diagnosis is the most essential prerequisite before beginning therapy. Most Alzheimer's patients' causes are still unclear, except for instances where hereditary variations have been noted. The gut microbiota composition significantly influences AD and any age-associated neurological illness. Therapies are very useful in improving the cognitive functions of AD. New microbiota-based therapy alternatives may now be available due to the more recent connection between the altered gut microbiome and neurodegeneration through the gut microbiota-brain axis.
PubMed: 37868425
DOI: 10.7759/cureus.45649 -
Biochemical Society Transactions Apr 2021Serpins (serine proteinase inhibitors) are an ancient superfamily of structurally similar proteins, the majority of which use an elegant suicide inhibition mechanism to... (Review)
Review
Serpins (serine proteinase inhibitors) are an ancient superfamily of structurally similar proteins, the majority of which use an elegant suicide inhibition mechanism to target serine proteinases. Despite likely evolving from a single common ancestor, the 36 human serpins have established roles regulating diverse biological processes, such as blood coagulation, embryonic development and extracellular matrix (ECM) turnover. Genetic mutations in serpin genes underpin a host of monogenic disorders - collectively termed the 'serpinopathies' - but serpin dysregulation has also been shown to drive pathological mechanisms in many common diseases. Osteoarthritis is a degenerative joint disorder, characterised by the progressive destruction of articular cartilage. This breakdown of the cartilage is driven by the metalloproteinases, and it has long been established that an imbalance of metalloproteinases to their inhibitors is of critical importance. More recently, a role for serine proteinases in cartilage destruction is emerging; including the activation of latent matrix metalloproteinases and cell-surface receptors, or direct proteolysis of the ECM. Serpins likely regulate these processes, as well as having roles beyond serine proteinase inhibition. Indeed, serpins are routinely observed to be highly modulated in osteoarthritic tissues and fluids by 'omic analysis, but despite this, they are largely ignored. Confusing nomenclature and an underappreciation for the role of serine proteinases in osteoarthritis (OA) being the likely causes. In this narrative review, serpin structure, biochemistry and nomenclature are introduced, and for the first time, their putative importance in maintaining joint tissues - as well as their dysregulation in OA - are explored.
Topics: Animals; Cartilage; Extracellular Matrix; Gene Expression Regulation; Humans; Metalloproteases; Multigene Family; Osteoarthritis; Protein Conformation; Serpins
PubMed: 33843993
DOI: 10.1042/BST20201231 -
Alcohol Research : Current Reviews 2024By 2040, 21.6% of Americans will be over age 65, and the population of those older than age 85 is estimated to reach 14.4 million. Although not causative, older age is a... (Review)
Review
PURPOSE
By 2040, 21.6% of Americans will be over age 65, and the population of those older than age 85 is estimated to reach 14.4 million. Although not causative, older age is a risk factor for dementia: every 5 years beyond age 65, the risk doubles; approximately one-third of those older than age 85 are diagnosed with dementia. As current alcohol consumption among older adults is significantly higher compared to previous generations, a pressing question is whether drinking alcohol increases the risk for Alzheimer's disease or other forms of dementia.
SEARCH METHODS
Databases explored included PubMed, Web of Science, and ScienceDirect. To accomplish this narrative review on the effects of alcohol consumption on dementia risk, the literature covered included clinical diagnoses, epidemiology, neuropsychology, postmortem pathology, neuroimaging and other biomarkers, and translational studies. Searches conducted between January 12 and August 1, 2023, included the following terms and combinations: "aging," "alcoholism," "alcohol use disorder (AUD)," "brain," "CNS," "dementia," "Wernicke," "Korsakoff," "Alzheimer," "vascular," "frontotemporal," "Lewy body," "clinical," "diagnosis," "epidemiology," "pathology," "autopsy," "postmortem," "histology," "cognitive," "motor," "neuropsychological," "magnetic resonance," "imaging," "PET," "ligand," "degeneration," "atrophy," "translational," "rodent," "rat," "mouse," "model," "amyloid," "neurofibrillary tangles," "α-synuclein," or "presenilin." When relevant, "species" (i.e., "humans" or "other animals") was selected as an additional filter. Review articles were avoided when possible.
SEARCH RESULTS
The two terms "alcoholism" and "aging" retrieved about 1,350 papers; adding phrases-for example, "postmortem" or "magnetic resonance"-limited the number to fewer than 100 papers. Using the traditional term, "alcoholism" with "dementia" resulted in 876 citations, but using the currently accepted term "alcohol use disorder (AUD)" with "dementia" produced only 87 papers. Similarly, whereas the terms "Alzheimer's" and "alcoholism" yielded 318 results, "Alzheimer's" and "alcohol use disorder (AUD)" returned only 40 citations. As pertinent postmortem pathology papers were published in the 1950s and recent animal models of Alzheimer's disease were created in the early 2000s, articles referenced span the years 1957 to 2024. In total, more than 5,000 articles were considered; about 400 are herein referenced.
DISCUSSION AND CONCLUSIONS
Chronic alcohol misuse accelerates brain aging and contributes to cognitive impairments, including those in the mnemonic domain. The consensus among studies from multiple disciplines, however, is that alcohol misuse can increase the risk for dementia, but not necessarily Alzheimer's disease. Key issues to consider include the reversibility of brain damage following abstinence from chronic alcohol misuse compared to the degenerative and progressive course of Alzheimer's disease, and the characteristic presence of protein inclusions in the brains of people with Alzheimer's disease, which are absent in the brains of those with AUD.
Topics: Humans; Dementia; Alcoholism; Aged; Animals; Aged, 80 and over; Alcohol Drinking; Brain; Alzheimer Disease; Risk Factors
PubMed: 38812709
DOI: 10.35946/arcr.v44.1.03 -
Frontiers in Aging Neuroscience 2022
PubMed: 36589547
DOI: 10.3389/fnagi.2022.1099417 -
Survey of Ophthalmology Apr 2024Neurotrophic keratopathy is an uncommon degenerative corneal disorder characterized by compromised corneal sensory innervation resulting in the formation of epithelial... (Review)
Review
Neurotrophic keratopathy is an uncommon degenerative corneal disorder characterized by compromised corneal sensory innervation resulting in the formation of epithelial defects and nonhealing corneal ulcers. Various treatment modalities are available to stabilize disease progression, improve patient well-being, and prevent vision loss. For eligible patients, medical and surgical reinnervation have emerged as pioneering therapies, holding promise for better management. We present a comprehensive review of the disorder, providing an update relevant to ophthalmologists on pathogenesis, diagnosis, treatment options, and novel therapies targeting pathophysiological pathways.
PubMed: 38679146
DOI: 10.1016/j.survophthal.2024.04.004 -
Frontiers in Pharmacology 2023Alzheimer's disease (AD) is the most common form of neurodegenerative disease and disability in the elderly; it is estimated to account for 60%-70% of all cases of... (Review)
Review
Alzheimer's disease (AD) is the most common form of neurodegenerative disease and disability in the elderly; it is estimated to account for 60%-70% of all cases of dementia worldwide. The most relevant mechanistic hypothesis to explain AD symptoms is neurotoxicity induced by aggregated amyloid-β peptide (Aβ) and misfolded tau protein. These molecular entities are seemingly insufficient to explain AD as a multifactorial disease characterized by synaptic dysfunction, cognitive decline, psychotic symptoms, chronic inflammatory environment within the central nervous system (CNS), activated microglial cells, and dysfunctional gut microbiota. The discovery that AD is a neuroinflammatory disease linked to innate immunity phenomena started in the early nineties by several authors, including the ICC´s group that described, in 2004, the role IL-6 in AD-type phosphorylation of tau protein in deregulating the cdk5/p35 pathway. The "Theory of Neuroimmunomodulation", published in 2008, proposed the onset and progression of degenerative diseases as a multi-component "damage signals" phenomena, suggesting the feasibility of "multitarget" therapies in AD. This theory explains in detail the cascade of molecular events stemming from microglial disorder through the overactivation of the Cdk5/p35 pathway. All these knowledge have led to the rational search for inflammatory druggable targets against AD. The accumulated evidence on increased levels of inflammatory markers in the cerebrospinal fluid (CSF) of AD patients, along with reports describing CNS alterations caused by senescent immune cells in neuro-degenerative diseases, set out a conceptual framework in which the neuroinflammation hypothesis is being challenged from different angles towards developing new therapies against AD. The current evidence points to controversial findings in the search for therapeutic candidates to treat neuroinflammation in AD. In this article, we discuss a neuroimmune-modulatory perspective for pharmacological exploration of molecular targets against AD, as well as potential deleterious effects of modifying neuroinflammation in the brain parenchyma. We specifically focus on the role of B and T cells, immuno-senescence, the brain lymphatic system (BLS), gut-brain axis alterations, and dysfunctional interactions between neurons, microglia and astrocytes. We also outline a rational framework for identifying "druggable" targets for multi-mechanistic small molecules with therapeutic potential against AD.
PubMed: 37361208
DOI: 10.3389/fphar.2023.1161850