A5014328017- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Tryptophan and brain disorders
- Nerve injury and regeneration
- Intensive Care Unit Cognitive Disorders
- Amyotrophic Lateral Sclerosis Research
- Biochemical effects in animals
- Gut microbiota and health
- Neurological Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Nuclear Receptors and Signaling
- Memory and Neural Mechanisms
- Diet and metabolism studies
- Retinal Development and Disorders
- Fatty Acid Research and Health
- Nutritional Studies and Diet
- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Immune Cell Function and Interaction
Emory University
1973-2024
Florida College
2020
University of Florida
2020
Alpha-synuclein aggregates (α-synAgg) are pathological hallmarks of Parkinson's disease (PD) and other synucleinopathies that induce microglial activation immune-mediated neurotoxicity, but the molecular mechanisms α-synAgg-induced immune poorly defined. We performed quantitative proteomics by mass spectrometry coupled with PCR, immunohistochemical functional validations studies to define characteristics alpha synuclein mediated activation. In mouse microglia, α-synAgg induced robust...
The etiology of sporadic Parkinson's disease (PD) remains uncertain, but genetic, epidemiological, and physiological overlap between PD inflammatory bowel suggests that gut inflammation could promote dysfunction dopamine-producing neurons in the brain. Mechanisms behind this pathological gut-brain effect their interactions with sex environmental factors are not well understood may represent targets for therapeutic intervention.We sought to identify active mechanisms which potentially...
Degeneration of locus Coeruleus (LC) neurons and dysregulation noradrenergic signaling are ubiquitous features Parkinson9s disease (PD). The LC is among the first brain regions affected by α-synuclein (asyn) pathology, yet how asyn affects these remains unclear. LC-derived norepinephrine (NE) can stimulate neuroprotective mechanisms modulate immune cells, while NE neurotransmission may exacerbate progression, particularly nonmotor symptoms, contribute to chronic neuroinflammation associated...
Introduction: Increasing evidence indicates that neurodegenerative diseases, including Alzheimer’s disease (AD), are a product of gene-by-environment interplay. The immune system is major contributor mediating these interactions. Signaling between peripheral cells and those within the microvasculature meninges central nervous (CNS), at blood-brain barrier, in gut likely plays an important role AD. cytokine tumor necrosis factor (TNF) elevated AD patients, regulates brain barrier...
The "shock and kill" strategy for HIV-1 cure incorporates latency-reversing agents (LRA) in combination with interventions that aid the host immune system clearing virally reactivated cells. LRAs have not yet been investigated pediatric clinical or preclinical studies. Here, we evaluated an inhibitor of apoptosis protein (IAP) (IAPi), AZD5582, activates noncanonical NF-κB (ncNF-κB) signaling pathway to reverse latency. Ten weekly doses AZD5582 were intravenously administered at 0.1 mg/kg...
Abstract Background Mutations in the progranulin gene ( GRN ) reduce levels of (PGRN) and granulins (GRNs) causing frontotemporal dementia (FTD), most common form early‐onset dementia. PGRN loss neurons is associated with lysosome dysfunction resulting diminished cathepsin protease activity. also highly expressed brain‐resident microglia peripheral immune cells. Therefore, we asked if impacts cell profiles communication gut‐brain axis during chronic systemic inflammation. Methods We measured...
Research into the disequilibrium of microglial phenotypes has become an area intense focus in neurodegenerative disease as a potential mechanism that contributes to chronic neuroinflammation and neuronal loss Parkinson's (PD). There is growing evidence accompanies may promote progression alpha-synuclein (Asyn)-induced nigral dopaminergic (DA) degeneration. From therapeutic perspective, development immunomodulatory strategies dampen overproduction pro-inflammatory cytokines from chronically...
Obesity and hypertension contribute to increased risk for neurodegenerative diseases, including Alzheimer's disease (AD). Peripheral inflammation, induced by unhealthy diet influences brain function, increases blood barrier (BBB) permeability, induces inflammation. However, the exact mechanism which chronic peripheral inflammation impacts AD-like pathology is unknown. Elevated levels of TNF in CSF plasma have been reported AD patients. promotes BBB altered regulation immune cell trafficking....
Peripheral immune cell signaling has been shown to play an important role in neuroinflammatory diseases, such as Alzheimer's disease (AD). Cytokine and chemokine mechanisms regulate peripheral trafficking inflamed tissues, the brain. The cytokine, soluble Tumor Necrosis Factor (solTNF), be elevated AD patients. SolTNF regulates blood-brain barrier permeability, is produced by central cells. Therefore, we hypothesize that sTNF a key mediator of contributions AD-like pathology. inflammation...
Mutations in the progranulin gene (GRN) reduce circulating levels of (PGRN) and granulins (GRNs) cause frontotemporal degeneration (FTD). PGRN is neuroprotective decreases amyloid β (Aβ) deposition APP mice. Strategies to increase have been proposed treat PGRN-deficient FTD Alzheimer's disease (AD). Although expressed neurons, also highly microglia other immune cells. Moreover, it unclear how loss cells affects neuronal survival. Therefore, we focused on understanding GRN all major subsets...
Peripheral immune cell signaling plays an important role in neurodegenerative diseases, such as Alzheimer's disease (AD) and a diet high fat sugar dysregulates several pathways that trigger metabolic responses worsen AD. Cytokine chemokine mechanisms regulate peripheral trafficking to inflamed tissues, including the gut brain. The cytokine, tumor necrosis factor (TNF), is elevated AD patients, regulates brain barrier permeability, produced by central cells. Further, TNF mediates conditions...
Abstract Background Sporadic Alzheimer’s disease (AD) is a product of complex gene‐environment (GxE) interactions. Central‐peripheral immune cell crosstalk and traffic across the blood‐brain barrier (BBB) have been implicated in AD pathophysiology by recent studies that demonstrate T‐cell signature brain, gut dysbiosis patients, significant epidemiological association between metabolic syndrome, obesity, type‐2 diabetes with increased incidence AD. Soluble tumor necrosis factor (sTNF), known...