A5039074744- Alzheimer's disease research and treatments
- Cholinesterase and Neurodegenerative Diseases
- Amyotrophic Lateral Sclerosis Research
- Neuroscience and Neuropharmacology Research
- Mitochondrial Function and Pathology
- Tryptophan and brain disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Nuclear Receptors and Signaling
- Parkinson's Disease Mechanisms and Treatments
- Computational Drug Discovery Methods
- Receptor Mechanisms and Signaling
- Autophagy in Disease and Therapy
- Prion Diseases and Protein Misfolding
- Nicotinic Acetylcholine Receptors Study
- CRISPR and Genetic Engineering
- Genetics and Neurodevelopmental Disorders
- Bacteriophages and microbial interactions
- Endoplasmic Reticulum Stress and Disease
- Neurogenetic and Muscular Disorders Research
- Neuropeptides and Animal Physiology
- Advanced Biosensing Techniques and Applications
- Genomics, phytochemicals, and oxidative stress
- Phosphodiesterase function and regulation
- biodegradable polymer synthesis and properties
- Trace Elements in Health
University of Messina
2023-2024
University of Catania
2014-2023
Arizona State University
2004-2020
Banner Sun Health Research Institute
2014-2015
The University of Texas Health Science Center at San Antonio
2009-2013
University of California, Irvine
2003-2011
Accumulation of amyloid-β (Aβ) and Tau is an invariant feature Alzheimer disease (AD). The upstream role Aβ accumulation in the pathogenesis widely accepted, there strong evidence showing that causes cognitive impairments. However, molecular mechanisms linking to decline remain be elucidated. Here we show buildup increases mammalian target rapamycin (mTOR) signaling, whereas decreasing mTOR signaling reduces levels, thereby highlighting interrelation between Aβ. pathway plays a central...
Accumulation of amyloid-beta (Abeta) is one the earliest molecular events in Alzheimer disease (AD), whereas tau pathology thought to be a later downstream event. It now well established that Abeta exists as monomers, oligomers, and fibrils. To study temporal profile oligomer formation vivo determine their interaction with pathology, we used 3xTg-AD mice, which develop progressive accumulation plaques tangles cognitive impairments. We show SDS-resistant oligomers accumulate an age-dependent...
Accumulation of tau is a critical event in several neurodegenerative disorders, collectively known as tauopathies, which include Alzheimer's disease and frontotemporal dementia. Pathological hyperphosphorylated aggregates to form neurofibrillary tangles. The molecular mechanisms leading accumulation remain unclear more needs be done elucidate them. Age major risk factor for all suggesting that changes contributing the aging process may facilitate represent common across different...
Neuronal Ca 2+ signaling through inositol triphosphate receptors (IP 3 R) and ryanodine (RyRs) must be tightly regulated to maintain cell viability, both acutely over a lifetime. Exaggerated intracellular levels have been associated with expression of Alzheimer's disease (AD) mutations in young mice, but little is known dysregulations during normal pathological aging processes. Here, we used electrophysiological recordings two-photon imaging study nontransgenic (NonTg) several AD mouse...
Accumulation of amyloid-β (Aβ) and fibrillary tangles, as well neuroinflammation memory loss, are hallmarks Alzheimer's disease (AD). After almost 15 years from their generation, 3xTg-AD mice still one the most used transgenic models AD. Converging evidence indicates that phenotype has shifted over contradicting reports about onset pathology or cognitive deficits apparent in literature. Here, we assessed Aβ tau load, neuroinflammation, changes 2-, 6-, 12-, 20-month-old female nontransgenic...
Increasing evidence points to soluble assemblies of aggregating proteins as a major mediator neuronal and synaptic dysfunction. In Alzheimer disease (AD), amyloid-beta (Abeta) appears be key factor in inducing cognitive abnormalities. Here we report the novel finding that tau also plays role decline presence concomitant Abeta pathology. We describe improved function following reduction both levels after active or passive immunization advanced aged 3xTg-AD mice contain amyloid plaques...
Disruptions in intracellular Ca 2+ signaling are proposed to underlie the pathophysiology of Alzheimer's disease (AD), and it has recently been shown that AD-linked mutations presenilin 1 gene ( PS1 ) enhance inositol triphosphate (IP 3 )-mediated liberation nonexcitable cells. However, little is known these actions neurons, which principal locus AD pathology. We therefore sought determine how affect signals their subsequent downstream effector functions cortical neurons. Using whole-cell...
Cognitive dysfunction and memory loss are common features of Alzheimer's disease (AD). Abnormalities in the expression profile immediate early genes that play a critical role formation, such as cAMP-response element binding protein (CREB), have been reported brains AD patients. Here we show amyloid-β (Aβ) accumulation, which plays primary cognitive deficits AD, interferes with CREB activity. We further restoring function via brain viral delivery CREB-binding (CBP) improves learning an animal...
The association between nicotinic acetylcholine receptor (nAChR) dysfunction and cognitive decline in Alzheimer's disease (AD) has been widely exploited for its therapeutic potential. effects of chronic nicotine exposure on Aβ accumulation have studied both humans animal models, but efficacy AD neuropathology is still unresolved. To date, no vivo studies addressed the consequences activating nAChRs tau pathology. determine administration pathology, we chronically administrated to a...
Understanding the factors that contribute to age-related cognitive decline is imperative, particularly as age major risk factor for several neurodegenerative disorders. Levels of cytokines increase in brain during aging, including IL-1β, whose levels positively correlate with deficits. Previous reports show reducing activity mammalian target rapamycin (mTOR) extends lifespan yeast, nematodes, Drosophila, and mice. It remains be established, however, whether extending accompanied by an...
Promising results have emerged from a phase II clinical trial testing methylene blue (MB) as potential therapeutic for Alzheimer disease (AD), where improvements in cognitive functions of AD patients after 6 months MB administration been reported. Despite these reports, no preclinical mammals has published, and thus its mechanism action relation to pathology remains unknown. In order elucidate the effects on determine action, we used mouse model (3xTg-AD) that develops age-dependent...
Elevated mammalian target of rapamycin (mTOR) signaling has been found in Alzheimer9s disease (AD) patients and is linked to diabetes aging, two known risk factors for AD. However, whether hyperactive mTOR plays a role the cognitive deficits associated with AD remains elusive. Here, we genetically reduced brains Tg2576 mice, widely used animal model We that suppression amyloid-β deposits rescued memory deficits. Mechanistically, reduction led an increase autophagy induction restored...
Reducing the mammalian target of rapamycin (mTOR) activity increases lifespan and health span in a variety organisms. Alterations protein homeostasis mTOR signaling have been reported several neurodegenerative disorders, including Alzheimer disease (AD); however, causes such deregulations remain elusive. Here, we show that are increased cell lines stably transfected with mutant amyloid precursor (APP) brains 3xTg-AD mice, an animal model AD. In addition, can be reduced to wild type levels by...
Aging is the major risk factor for several neurodegenerative diseases, including Alzheimer's disease (AD). However, mechanisms by which aging contributes to neurodegeneration remain elusive. The nuclear (erythroid-derived 2)-like 2 (Nrf2) a transcription that regulates expression of vast number genes binding antioxidant response element. Nrf2 levels decrease as function age, and reduced have been reported in postmortem human brains animal models AD. Nevertheless, it still unknown whether...
There is an urgent need for the development of new therapeutic strategies Alzheimer's disease (AD). The dual-specificity tyrosine phosphorylation-regulated kinase-1A (Dyrk1a) a protein kinase that phosphorylates amyloid precursor (APP) and tau thus represents link between two key proteins involved in AD pathogenesis. Furthermore, Dyrk1a upregulated postmortem human brains, high levels are associated with mental retardation. Here, we sought to determine effects Dyrk1 inhibition on AD-like...
Aging is the most important risk factor associated with Alzheimer's disease (AD); however, molecular mechanisms linking aging to AD remain unclear. Suppression of ribosomal protein S6 kinase 1 (S6K1) increases healthspan and lifespan in several organisms, from nematodes mammals. Here we show that S6K1 expression upregulated brains patients. Using a mouse model AD, found genetic reduction improved synaptic plasticity spatial memory deficits, reduced accumulation amyloid-β tau, two...