A5026884148- Alzheimer's disease research and treatments
- Cholinesterase and Neurodegenerative Diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Eicosanoids and Hypertension Pharmacology
- Renin-Angiotensin System Studies
- Neurological Disease Mechanisms and Treatments
- Cellular transport and secretion
- Tryptophan and brain disorders
- Nitric Oxide and Endothelin Effects
- MicroRNA in disease regulation
- Ion Channels and Receptors
- Cerebrovascular and Carotid Artery Diseases
- Nuclear Receptors and Signaling
- Adipose Tissue and Metabolism
- Biochemical effects in animals
- Cell Adhesion Molecules Research
- Extracellular vesicles in disease
- Retinoids in leukemia and cellular processes
- Neurobiology and Insect Physiology Research
- RNA regulation and disease
- Biochemical Analysis and Sensing Techniques
- Barrier Structure and Function Studies
- Immune cells in cancer
- PI3K/AKT/mTOR signaling in cancer
University of Tennessee Health Science Center
2016-2025
Indiana University Bloomington
2024
Massachusetts General Hospital
2024
Tulane University
2024
The University of Texas Health Science Center at Houston
2021
University of Memphis
2020
Sanford Burnham Prebys Medical Discovery Institute
2006-2009
Institute for Medical Research
2006-2009
The incidence of Alzheimer disease (AD) and vascular dementia is greatly increased following cerebral ischemia stroke in which hypoxic conditions occur affected brain areas. β-Amyloid peptide (Aβ), derived from the β-amyloid precursor protein (APP) by sequential proteolytic cleavages β-secretase (BACE1) presenilin-1 (PS1)/γ-secretase, widely believed to trigger a cascade pathological events culminating AD dementia. However, direct molecular link between insults APP processing has yet be...
Epidemiological, clinical and experimental evidence suggests a link between type 2 diabetes Alzheimer's disease (AD). Insulin modulates metabolism of β-amyloid precursor protein (APP) in neurons, decreasing the intracellular accumulation (Aβ) peptides, which are pivotal AD pathogenesis. The present study investigates whether widely prescribed insulin-sensitizing drug, metformin (Glucophage R ), affects APP Aβ generation various cell models. We demonstrate that metformin, at doses lead to...
Neuroinflammation is implicated in the development and progression of many neurodegenerative diseases. Conditions that lead to a peripheral immune response are often associated with inflammation central nervous system (CNS), suggesting communication between neuroimmune system. The underlying mechanism this relationship remains largely unknown; however, experimental studies have demonstrated exposure infectious stimuli, such as lipopolysaccharide (LPS) or high-fat diet (HFD) feeding, result...
Presenilins (PS, PS1/PS2) are necessary for the proteolytic activity of gamma-secretase, which cleaves multiple type I transmembrane proteins including Alzheimer's beta-amyloid precursor protein (APP), Notch, ErbB4, etc. Cleavage by PS/gamma-secretase releases intracellular domain (ICD) its substrates. Notch ICD translocates into nucleus to regulate expression genes important development. However, patho/physiological role other ICDs, especially APP (AICD), in regulating gene remains...
The phosphatase PTEN governs the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway which is arguably most important pro-survival in neurons. Recently, has also been implicated multiple CNS functions such as neuronal differentiation, plasticity, injury and drug addiction. It reported that loss of protein, accompanied by Akt activation, occurs under excitotoxic conditions (stroke) well Alzheimer's (AD) brains. However molecular signals mechanism underlying are unknown.In this study, we...
The excessive accumulation of soluble amyloid peptides (Aβ) plays a crucial role in the pathogenesis Alzheimer's disease (AD), particularly synaptic dysfunction. two major chaperone proteins, Hsp70 and Hsp90, clearing misfolded protein aggregates has been established. Despite their abundant presence synapses, these chaperones synapses remains elusive. Here, we report that Hsp90 inhibition by 17-AAG elicited not only heat shock-like response but also upregulated presynaptic postsynaptic such...
Cerebral infarction due to thrombosis leads the most common type of stroke and a likely cause age-related cognitive decline dementia. Endothelial nitric oxide synthase (eNOS) generates NO, which plays crucial role in maintaining vascular function exerting an antithrombotic action. Reduced eNOS expression polymorphisms have been associated with Alzheimer's disease (AD), dementia neurovascular dysfunction. However, direct proof such association is lacking. Since there are no reports complete...
Alzheimer's disease (AD) is the most common form of age-associated dementia characterized by amyloid-β plaques and neurofibrillary tangles. Recent studies have demonstrated that thioredoxin-interacting protein (TXNIP), an endogenous regulator redox/glucose induced stress inflammation, now known to be upregulated in stroke, traumatic brain injury, diabetes AD. We hypothesized TXNIP overexpression sustains neurodegeneration through activation nucleotide binding oligomerization domain-like...
It is well established that both cerebral hypoperfusion/stroke and type 2 diabetes are risk factors for Alzheimer's disease (AD). Recently, the molecular link between ischemia/hypoxia amyloid precursor protein (APP) processing has begun to be established. However, role of key common denominator, namely nitric oxide (NO), in AD largely unknown. In this study, we investigated redox regulation BACE1, rate-limiting enzyme responsible β-cleavage APP Aβ peptides.Herein, studied events such as...
Insulin resistance and neuroinflammation have emerged as two likely key contributors in the pathogenesis of Alzheimer disease (AD), especially those sporadic AD cases compromised by diabetes or cardiovascular disease. Amyloid-β (Aβ) deposition its associated inflammatory response are hallmarks brains. Elevated expression activity β-secretase 1 (BACE1), rate-limiting enzyme responsible for β-cleavage amyloid precursor proteins to Aβ peptides, also observed Previous studies suggested that...
Vascular cognitive impairment and dementia (VCID) is the second most common form of after Alzheimer's disease (AD). Currently, mechanistic insights into evolution progression VCID remain elusive. White matter change represents an invariant feature. Compelling clinical neuroimaging pathological evidence suggest a link between white changes neurodegeneration. Our prior study detected hypoperfused lesions in mice with partial deficiency endothelial nitric oxide (eNOS) at very young age,...
Recent studies indicate that soluble β-amyloid (sAβ) oligomers, rather than their fibrillar aggregates, contribute to the pathogenesis of Alzheimer's disease (AD), though mechanisms neurotoxicity are still elusive. Here, we demonstrate sAβ derived from 7PA2 cells exert a much stronger effect on regulation set functionally validated microRNAs (miRNAs) in primary cultured neurons synthetic insoluble Aβ fibrils (fAβ). Synthetic peptides at higher concentration present comparable these miRNAs...
Abstract Sepsis-associated encephalopathy (SAE) is an acutely progressing brain dysfunction induced by systemic inflammation. The mechanism of initiation neuroinflammation during SAE, which ultimately leads to delirium and cognitive dysfunction, remains elusive. We aimed study the molecular events SAE capture its onset progression into central nervous system (CNS), further identify cellular players involved in mediating acute inflammatory signaling. Gene expression profiling on cerebral...
Abstract Tauopathies are neurodegenerative diseases that pathologically characterized by accumulation of misfolded microtubule-associated protein tau aggregates in the brain. Deubiquitination, particularly OTULIN, a unique deubiquitinase targeting methionine-1 (M1) linkages from linear ubiquitin chain assembly complex (LUBAC)), is reportedly associated with neurotoxic proteins several diseases, likely including tauopathies. To investigate potential roles OTULIN tauopathies, we analyzed...
Alzheimer's disease is cytopathologically characterized by loss of synapses and neurons, neuritic amyloid plaques consisting β-amyloid (Aβ) peptides, neurofibrillary tangles hyperphosphorylated tau protein in susceptible brain regions. Aβ, which triggers a cascade pathogenic events including phosphorylation neuronal excitotoxicity, proteolytically derived from precursor (APP); the pathological physiological functions APP, however, remain undefined. Here we demonstrate that level cells brains...
Neurofibrillary tangles (NFTs), consisting of abnormally hyperphosphorylated tau, are implicated in the pathogenesis several neurodegenerative diseases including Alzheimer's disease (AD). The molecular mechanisms underlying regulation tau phosphorylation largely unknown. While PI3K/Akt pathway has been shown to regulate multiple cellular events pertinent AD pathogenesis, potential functions tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) have not explored....
The contribution of zinc-mediated neuronal death in the process both acute and chronic neurodegeneration has been increasingly appreciated. Phosphatase tensin homologue, deleted on chromosome 10 (PTEN), major tumor suppressor key regulator phosphatidylinositol 3-kinase (PI3K)/Akt pathway, plays a critical role response to various insults. NEDD4-1-mediated PTEN ubiquitination subsequent degradation via ubiquitin proteosomal system have recently demonstrated be important regulatory mechanism...
The widely used cholesterol-lowering drugs, statins, were reported to reduce the incidence of stroke and progression Alzheimer's disease. However, little is known on how statins exert these beneficial effects. In this study, we investigated molecular mechanisms underlying neuroprotective actions in primary cultured cortical neurons. We found that chronic treatment neurons with a low dosage two CNS-permeable (lovastatin simvastatin) selectively reduced NMDA-induced cell death but not...
Excessive accumulation of beta-amyloid peptides in the brain is a major cause for pathogenesis Alzheimer disease. beta-Amyloid derived from precursor protein (APP) through sequential cleavages by beta- and gamma-secretases, whose enzymatic activities are tightly controlled subcellular localization. Delineation how intracellular trafficking these secretases APP regulated important understanding disease pathogenesis. Although multiple factors including presenilin 1 (PS1), component...
Immune system hypersensitivity is believed to contribute mental frailty in the elderly. Solid evidence indicates NOD-like receptor pyrin domain containing-3 (NLRP3)-inflammasome activation intimately connects aging-associated chronic inflammation (inflammaging) senile cognitive decline. Thioredoxin interacting protein (TXNIP), an inducible involved oxidative stress, essential for NLRP3 inflammasome activity. This study aims find whether TXNIP/NLRP3 pathway dementia. According our studies on...