Shifts in normal aging set stage for neurodegeneration and dementia affecting 1 in 10 adults. The study demonstrates that lncRNA GAS5 is decreased in aged and Alzheimer's disease brain. The role and targets of lncRNA GAS5 in the aging brain were elucidated using a GAS5-targeting small molecule NPC86, a frontier in lncRNA-targeting therapeutic.
View Article and Find Full Text PDFThe neuroprotective role of human adipose-derived stems cells (hASCs) has raised great interest in regenerative medicine due to their ability to modulate their surrounding environment. Our group has demonstrated that exosomes derived from hASC (hASCexo) are a cell-free regenerative approach to long term recovery following traumatic brain injury (TBI). Previously, we demonstrated the efficacy of exosome treatment with intravenous delivery at 3 h post TBI in rats.
View Article and Find Full Text PDFMicroglial activity in the aging neuroimmune system is a central player in aging-related dysfunction. Aging alters microglial function via shifts in protein signaling cascades. These shifts can propagate neurodegenerative pathology.
View Article and Find Full Text PDFBackground: Parkinson's disease (PD) is the second most prevalent movement disorder characterized by up to 80% loss of dopamine (DA) neurons and accumulation of Lewy body deposits composed of α-synuclein (α-syn). Accumulation of α-syn is associated with microglial activation, leading to a pro-inflammatory environment linked with the pathogenesis of PD. Along with microglia, CD4 and CD8 T cells are observed in SNpc.
View Article and Find Full Text PDFAging is associated with many pathophysiological changes that could lead to the onset of degenerative disease. Some of the physiological changes that occur with aging include increased inflammation and decreased stem cell proliferation, leading to decreased capacity for tissue regeneration and loss of function. In previous studies, we and others have found nutraceutical intervention to ameliorate some of the deleterious effects associated with aging.
View Article and Find Full Text PDFEur J Mass Spectrom (Chichester)
June 2020
The question of whether [CHOH] should be described as the hydroxymethyl cation, CHOH, or protonated formaldehyde, CH=OH, is reconsidered in the light of experimental information and new computational evidence. Previous arguments that the charge distribution in [CHOH] may be probed by considering the incremental stabilisation of [CHOH] induced by homologation on carbon (to give [CHCHOH]) or oxygen (to produce [CHOCH]) are critically examined. Cation stabilisation energies are shown to be better indicators of the nature of these oxonium ions.
View Article and Find Full Text PDFThe incidence of neurodegenerative disorders and cognitive impairment is increasing. Rising prevalence of age-related medical conditions is associated with a dramatic economic burden; therefore, developing strategies to manage these health concerns is of great public health interest. Nutritionally based interventions have shown promise in treatment of these age-associated conditions.
View Article and Find Full Text PDFBackground: Neuroinflammation is a common therapeutic target for traumatic brain injury (TBI) due to its contribution to delayed secondary cell death and has the potential to occur for years after the initial insult. Exosomes from adipose-derived stem cells (hASCs) containing the long noncoding RNA MALAT1 are a novel, cell-free regenerative approach to long-term recovery after traumatic brain injury (TBI) that have the potential to modulate inflammation at the genomic level. The long noncoding RNA MALAT1 has been shown to be an important component of the secretome of hASCs.
View Article and Find Full Text PDFThe prevalence of HIV-associated neurocognitive disorders (HAND) remains high despite combination antiretroviral therapy (cART). There is evidence that neural stem cells (NSCs) can migrate to sites of brain injury such as those caused by inflammation and oxidative stress, which are pathological features of HAND. Thus, reductions in NSCs may contribute to HAND pathogenesis.
View Article and Find Full Text PDFJ Neuroinflammation
September 2015
Background: Aging is associated with a decline in stem cell proliferation that is thought to be a result of dysregulated signaling in the neurogenic niche. This results in a diminished and less efficient pool of progenitors. The Wnt pathway plays a key role in the proliferation and differentiation of progenitor cells.
View Article and Find Full Text PDFThe protein α-synuclein (α-Syn) has a central role in the pathogenesis of Parkinson's disease (PD) and immunotherapeutic approaches targeting this molecule have shown promising results. In this study, novel antibodies were generated against specific peptides from full length human α-Syn and evaluated for effectiveness in ameliorating α-Syn-induced cell death and behavioral deficits in an AAV-α-Syn expressing rat model of PD. Fisher 344 rats were injected with rAAV vector into the right substantia nigra (SN), while control rats received an AAV vector expressing green fluorescent protein (GFP).
View Article and Find Full Text PDFIn Parkinson's disease, α-synuclein is known to activate microglia and this activation has been proposed as one of the mechanisms of neurodegeneration. There are several signals produced by neurons that have an anti-inflammatory action on microglia, including CX3CL1 (fractalkine). We have shown that a soluble form of CX3CL1 is required to reduce neuron loss in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice and that fractalkine agonism can reduce neuron loss in a 6-hydroxydopamine lesion model.
View Article and Find Full Text PDFAims: To describe the availability of aged care and dementia services in public hospitals in New South Wales (NSW), Australia in 2006/2007.
Method: Hospitals were surveyed about issues relevant to dementia in acute care including the types of aged care wards and staff, policies, practices, clinics, community services and resources for dementia care.
Results: Responses were obtained from 163 hospitals (82%); responding hospitals represented 93.
Frequent monitor alarms are distracting and interfere with clinicians performing critical tasks. This article describes a quality improvement rapid-cycle change approach to explore the benefits of changing electrodes daily on the number of cardiac monitor alarms. Eight days of baseline and intervention data were compared for 2 adult acute care units.
View Article and Find Full Text PDFInflammation in the brain plays a major role in neurodegenerative diseases. In particular, microglial cell activation is believed to be associated with the pathogenesis of neurodegenerative diseases, including Parkinson's disease (PD). An increase in microglia activation has been shown in the substantia nigra pars compacta (SNpc) of PD models when there has been a decrease in tyrosine hydroxylase (TH) positive cells.
View Article and Find Full Text PDFHigh-potency topical corticosteroids are the cornerstone of psoriasis therapy. Although highly effective, long-term use of topical steroids can cause adverse side effects. Additionally, steroids alone do not address the multiple pathophysiologic factors that cause the disease.
View Article and Find Full Text PDFThe protective/neurotoxic role of fractalkine (CX3CL1) and its receptor CX3C chemokine receptor 1 (CX3CR1) signaling in neurodegenerative disease is an intricate and highly debated research topic and it is becoming even more complicated as new studies reveal discordant results. It appears that the CX3CL1/CX3CR1 axis plays a direct role in neurodegeneration and/or neuroprotection depending on the CNS insult. However, all the above studies focused on the role of CX3CL1/CX3CR1 signaling in pathological conditions, ignoring the relevance of CX3CL1/CX3CR1 signaling under physiological conditions.
View Article and Find Full Text PDFPsoriasis is a chronic condition with serious quality-of-life ramifications. Dermatologists seek alternative treatments of patients with plaque psoriasis that provide both efficacy and safety while minimizing exposure to high-potency steroids that can have adverse effects following long-term use. We report an open-label, multicenter study designed to evaluate a morning/evening (AM/PM) treatment regimen involving clobetasol propionate spray 0.
View Article and Find Full Text PDFBackground: Clobetasol propionate 0.05% spray is available for treating moderate-to-severe plaque psoriasis; however, there is limited information with plaque psoriasis of the scalp.
Objective: Evaluate the efficacy, safety, and quality-of-life impact of clobetasol propionate 0.
Background: Psoriasis is a hyperproliferative and inflammatory skin disorder that affects roughly 2 percent of the worldwide population. Clobetasol propionate is the most common corticosteroid used to treat moderate-to-severe psoriasis but the potential for side effects limits its long-term use. Topical vitamin D, which is used to treat mild-to-moderate psoriasis, has been shown to be safe when used daily for up to 52 weeks.
View Article and Find Full Text PDFBackground: Parkinson's disease is characterized by a progressive loss of dopaminergic neurons in the substantia nigra. The cause of the neurodegeneration is unknown. Neuroinflammation has been clearly shown in Parkinson's disease and may be involved in the progressive nature of the disease.
View Article and Find Full Text PDFAdult stem cells are present in many tissues including, skin, muscle, adipose, bone marrow, and in the brain. Neuroinflammation has been shown to be a potent negative regulator of stem cell and progenitor cell proliferation in the neurogenic regions of the brain. Recently we demonstrated that decreasing a key neuroinflammatory cytokine IL-1beta in the hippocampus of aged rats reversed the age-related cognitive decline and increased neurogenesis in the age rats.
View Article and Find Full Text PDFMicroglia have neuroprotective capacities, yet chronic activation can promote neurotoxic inflammation. Neuronal fractalkine (FKN), acting on CX(3)CR1, has been shown to suppress excessive microglia activation. We found that disruption in FKN/CX(3)CR1 signaling in young adult rodents decreased survival and proliferation of neural progenitor cells through IL-1β.
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