A5058693947- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Visual perception and processing mechanisms
- Neurological disorders and treatments
- Neural and Behavioral Psychology Studies
- Neural dynamics and brain function
- Nuclear Receptors and Signaling
- Memory and Neural Mechanisms
- Computational Drug Discovery Methods
- Botulinum Toxin and Related Neurological Disorders
- Cholinesterase and Neurodegenerative Diseases
- Cancer Treatment and Pharmacology
- Insect and Arachnid Ecology and Behavior
- Neurobiology and Insect Physiology Research
- Prion Diseases and Protein Misfolding
- RNA Interference and Gene Delivery
- Neurological Disease Mechanisms and Treatments
- Neurological diseases and metabolism
- Motor Control and Adaptation
- Single-cell and spatial transcriptomics
- Stress Responses and Cortisol
- Phytochemical Studies and Bioactivities
- Calpain Protease Function and Regulation
National Institute on Aging
2018-2025
National Institutes of Health
2018-2024
Institute on Aging
2010-2021
University of Pennsylvania
2007-2017
Institute for Neurodegenerative Disorders
2011-2017
Tamagawa University
2008-2011
Hospital of the University of Pennsylvania
2011
Philadelphia University
2007
Japan Science and Technology Agency
2001-2003
Hokkaido University
1995-2003
Tauopathies, including Alzheimer's disease (AD) and frontotemporal lobar degeneration with tau pathologies, are neurodegenerative diseases characterized by neurofibrillary tangles (NFTs) comprising filamentous protein. Although emerging evidence suggests that pathology may be transmitted, we demonstrate here synthetic fibrils sufficient to transmit inclusions in a mouse model. Specifically, intracerebral inoculation of young PS19 mice overexpressing mutant human (P301S) preformed (pffs)...
Filamentous tau aggregates are hallmark lesions in numerous neurodegenerative diseases, including Alzheimer’s disease (AD). Cell culture and animal studies showed that fibrils can undergo cell-to-cell transmission seed aggregation of soluble tau, but this phenomenon was only robustly demonstrated models overexpressing tau. In study, we found intracerebral inoculation purified from AD brains (AD-tau), not synthetic fibrils, resulted the formation abundant inclusions anatomically connected...
Neurodegenerative tauopathies, such as Alzheimer's disease (AD), are characterized by insoluble deposits of hyperphosphorylated tau protein within brain neurons. Increased phosphorylation and decreased solubility has been proposed to diminish normal stabilization microtubules (MTs), thereby leading neuronal dysfunction. Earlier studies have provided evidence that small molecule MT-stabilizing drugs used in the treatment cancer may utility tauopathies. However, it not established whether with...
Neurons in the brains of those with Alzheimer's disease (AD) and many frontotemporal dementias (FTDs) contain neurofibrillary tangles comprised hyperphosphorylated tau protein. Tau normally stabilizes microtubules (MTs), misfolding could lead to a loss this function consequent MT destabilization neuronal dysfunction. Accordingly, possible therapeutic strategy for AD related "tauopathies" is treatment MT-stabilizing anti-cancer drug such as paclitaxel. However, paclitaxel taxanes have poor...
Because overactivation of the hypothalamic–pituitary–adrenal (HPA) axis occurs in Alzheimer's disease (AD), dysregulation stress neuromediators may play a mechanistic role pathophysiology AD. However, effects on tau phosphorylation are poorly understood, and relationship between corticosterone corticotropin-releasing factor (CRF) both β-amyloid (Aβ) pathology remain unclear. Therefore, we first established model chronic stress, which exacerbates Aβ accumulation Tg2576 mice then extended this...
Tauopathies are neurodegenerative disorders characterized by the accumulation of abnormal tau protein leading to cognitive and/or motor dysfunction. To understand relationship between pathology and behavioral impairments, we comprehensively assessed abnormalities in a mouse tauopathy model expressing human P301S mutant early stage disease detect its initial neurological manifestations. Behavioral abnormalities, shown open field test, elevated plus-maze hot plate Y-maze Barnes maze Morris...
Synucleinopathies of the aging population are an heterogeneous group neurological disorders that includes Parkinson's disease (PD) and dementia with Lewy bodies (DLB) characterized by progressive accumulation α-synuclein in neuronal glial cells. Toll-like receptor 2 (TLR2), a pattern recognition immune receptor, has been implicated pathogenesis synucleinopathies because TLR2 is elevated brains patients PD mediator neurotoxic pro-inflammatory effects extracellular aggregates. Therefore,...
Abstract Background α-Synuclein (α-syn) is a pre-synaptic protein which progressively accumulates in neuronal and non-neuronal cells neurodegenerative diseases such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy. Recent evidence suggests that aberrant immune activation may be involved neurodegeneration PD/DLB. While previous studies have often focused on the microglial responses, less known about role of peripheral these disorders. Methods To understand...
Highlights•Generation of a foundational genomic resource in multiple system atrophy•GWAS identifies novel risk loci at GAB1, lnc-LRRC49-3, TENM2, and RABGEF1•Functional genomics implicates USP38-DT, KCTD7, lnc-KCTD7-2 within these loci•Gene-burden analysis nominal enrichment rare missense mutations KCTD7SummaryMultiple atrophy (MSA) is an adult-onset, sporadic synucleinopathy characterized by parkinsonism, cerebellar ataxia, dysautonomia. The genetic architecture MSA poorly understood,...
LRRK2 modulates nucleus translocation of NFATc2 in microglia.
Alterations in the p38 mitogen-activated protein kinases (MAPKs) play an important role pathogenesis of dementia with Lewy bodies (DLB) and Parkinson's disease (PD). Activation p38α MAPK isoform mislocalization p38γ are associated neuroinflammation synaptic degeneration DLB PD. Therefore, we hypothesized that might be neuronal distribution dysfunction these diseases. To test this hypothesis, treated vitro cellular vivo mouse models DLB/PD SKF-86002, a compound attenuates inflammation by...
In primates, dorsolateral areas of the prefrontal cortex (PFC) play a major role in visuospatial working memory. To examine functional organization PFC for representing memory, we produced reversible local inactivation, with injection muscimol (5 μg, 1 μl), at various sites ( n = 100) monkeys and observed behavioral consequences an oculomotor delayed-response task that required memory-guided saccades locations throughout both visual fields. At 82 sites, induced deficits to few specific,...
Tauopathies are neurodegenerative disorders characterized by abnormal intracellular aggregates of tau protein, and include Alzheimer's disease, corticobasal degeneration, frontotemporal dementia, traumatic brain injury. Glutamate metabolism is altered in manifesting higher or lower concentrations glutamate, its transporters receptors. Previously, glutamate chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI) demonstrated that levels reduced regions synapse loss...
Abstract Background Although ɑ-synuclein (ɑ-syn) spreading in age-related neurodegenerative diseases such as Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB) has been extensively investigated, the role of aging manifestation remains unclear. Methods We explored inflammation pathogenesis synucleinopathies a mouse model DLB/PD initiated by intrastriatal injection ɑ-syn preformed fibrils (pff). Results found that aged mice showed more extensive accumulation selected brain regions...
Abstract Synucleinopathies are age-related neurological disorders characterized by the progressive deposition of α-synuclein (α-syn) aggregates and include Parkinson’s disease (PD) dementia with Lewy bodies (DLB). Although cell-to-cell α-syn transmission is thought to play a key role in spread pathology, detailed mechanism still unknown. Neuroinflammation another pathological feature synucleinopathies. Previous studies have identified several immune receptors that mediate neuroinflammation...
We examined quantitative changes in biogenic amines relation to effects of population density on growth and behavior the cricket Gryllus bimaculatus, which were reared two different densities, completely isolated solitary 40 crowded insects. In animals, rate increase body weight was slow, also day imaginal moult late, when compared ones. Development thus suppressed group. The color ones darker than that Behavioral tests indicated crickets significantly more aggressive levels amines, their...