A5016355760- Alzheimer's disease research and treatments
- RNA regulation and disease
- Parkinson's Disease Mechanisms and Treatments
- RNA Research and Splicing
- Acute Myeloid Leukemia Research
- Multiple Myeloma Research and Treatments
- HIV Research and Treatment
- Protein Degradation and Inhibitors
- RNA Interference and Gene Delivery
- Nuclear Receptors and Signaling
- Cholinesterase and Neurodegenerative Diseases
- Neurological Disorders and Treatments
- Virus-based gene therapy research
- interferon and immune responses
- Neuroscience and Neuropharmacology Research
- Genetics and Neurodevelopmental Disorders
- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Chronic Myeloid Leukemia Treatments
- CRISPR and Genetic Engineering
- Viral Infections and Immunology Research
- Ocular Surface and Contact Lens
- Nerve injury and regeneration
- Peptidase Inhibition and Analysis
- Ubiquitin and proteasome pathways
University of California, San Diego
2014-2025
Sanford Consortium for Regenerative Medicine
2012-2024
Moores Cancer Center
2012-2023
University of Oxford
2012
Alcon (United States)
2012
University of Louisville
2012
Georgetown University
2012
Stem Cell Institute
2012
Nathan Kline Institute for Psychiatric Research
2008
Neurobehavioral Research (United States)
2006
Neuronal accumulation of alpha-synuclein and Lewy body formation are characteristic to many neurodegenerative diseases, including Parkinson's disease (PD). This pathology appears spread throughout the brain as progresses. Furthermore, recent studies showed occurrence in neurons grafted into brains PD patients, suggesting from host tissues grafts. The mechanism underlying this propagation is unknown. Here, we show that transmitted via endocytosis neighboring neuronal precursor cells, forming...
To evaluate in a general clinic-based cohort of patients with dry eye disease (DED) the distribution aqueous-deficient or evaporative subtype DED.Schirmer tests and meibomian gland dysfunction (MGD) (Foulks-Bron scoring) were evaluated both eyes 299 normal subjects DED (218 women 81 men) across 10 sites European Union United States. Using more severe measurement 2 eyes, considered to have pure (ADDE) Schirmer values <7 mm MGD grades ≤5. Patients classified as purely >5 ≥7 mm. Subjects placed...
Dementia with Lewy bodies (DLB) and Parkinson's Disease (PD) are common causes of motor cognitive deficits associated the abnormal accumulation alpha-synuclein (α-syn). This study investigated whether passive immunization a novel monoclonal α-syn antibody (9E4) against C-terminus (CT) was able to cross into CNS ameliorate accumulation. In this we demonstrate that 9E4 effective at reducing behavioral in water maze, moreover, reduced calpain-cleaved axons synapses neurodegenerative deficits....
Lewy body disease is a heterogeneous group of neurodegenerative disorders characterized by alpha-synuclein accumulation that includes dementia with bodies (DLB) and Parkinson's Disease (PD). Recent evidence suggests impairment lysosomal pathways (i.e. autophagy) involved in clearance might play an important role. For this reason, we sought to examine the expression levels members autophagy pathway brains patients DLB Alzheimer's (AD) transgenic mice.
The authors report a patient with Alzheimer disease (AD) without encephalitis who was immunized AN-1792 (an adjuvanted formulation of Abeta-42). There were no amyloid plaques in the frontal cortex and abundant Abeta-immunoreactive macrophages, but tangles angiopathy present. white matter appeared normal minimal lymphocytic infiltration leptomeninges observed. This case illustrates effects an Abeta-based immunization on AD pathogenesis absence overt meningoencephalitis leukoencephalopathy.
Abstract. Purpose: To evaluate the relationship between signs and symptoms of dry eye disease (DED) in a clinic‐based population. Methods: In retrospective analysis, clinical were evaluated for 344 subjects ( n = 82, normal; 263, eye), across 11 sites from EU United States. Pearson correlations r 2 ) an independent components analysis (ICA) mixing matrix derived data set. Similar was performed on set 200 previous study Munich, Germany. Results: No above 0.17 found any symptoms, except...
Alzheimer’s disease (AD) is characterized by progressive neurodegeneration and cerebral accumulation of the β-amyloid peptide (Aβ), but it unknown what makes neurons susceptible to degeneration. We report that TGF-β type II receptor (TβRII) mainly expressed neurons, TβRII levels are reduced in human AD brain correlate with pathological hallmarks disease. Reducing neuronal signaling mice resulted age-dependent promoted Aβ dendritic loss a mouse model AD. In cultured cells, caused degeneration...
The glycogen synthase kinase-3β (GSK3β) pathway plays an important role in mediating neuronal fate and synaptic plasticity. In Alzheimer's disease (AD), abnormal activation of this might play neurodegeneration, compounds such as lithium that modulate GSK3β activity have been shown to reduce amyloid production tau phosphorylation precursor protein (APP) transgenic (tg) mice. However, it is unclear whether regulation neuroprotective APP tg context, the main objective present study was...
Misfolding and pathological aggregation of neuronal proteins has been proposed to play a critical role in the pathogenesis neurodegenerative disorders. Alzheimer's disease (AD) Parkinson's (PD) are frequent diseases aging population. While progressive accumulation amyloid beta protein (Abeta) oligomers identified as one central toxic events AD, alpha-synuclein (alpha-syn) resulting formation protofibrils linked PD Lewy body Disease (LBD). We have recently shown that Abeta promotes alpha-syn...
Multiple system atrophy (MSA) is a progressive, neurodegenerative disease characterized by parkinsonism, ataxia, autonomic dysfunction, and accumulation of α-synuclein (α-syn) in oligodendrocytes. To better understand the mechanisms neurodegeneration role α-syn oligodendrocytes pathogenesis MSA, we generated transgenic mouse lines expressing human (h) under control murine myelin basic protein promoter. Transgenic mice high levels hα-syn displayed severe neurological alterations died...
The cognitive impairment in patients with Alzheimer's disease is closely associated synaptic loss the neocortex and limbic system. Although neurotoxic effects of aggregated amyloid-beta oligomers have been studied extensively experimental models, less known about characteristics these aggregates across spectrum disease. In this study, postmortem frontal cortex samples from controls were fractionated analyzed for levels proteins. We found that correlated severity (blessed...
During aging and in the progression of Alzheimer's disease (AD), synaptic plasticity neuronal integrity are disturbed. In addition to alterations mature neurons, neurodegenerative process AD has been shown be accompanied by neurogenesis. Members bone morphogenetic protein (BMP) family growth factors have implicated as important regulators neurogenesis cell fate determination during development; however, their role adult is less clear. We show here qRT-PCR analysis that BMP6 mRNA levels were...
Purpose: To evaluate the efficacy of commonly used biomarkers in dry eye disease management a longitudinal observational case series study followed by an interventional subset subjects treated with cyclosporine A (0.05%). Methods: Bilateral tear osmolarity, Schirmer, film breakup time (TBUT), staining, meibomian grading, and Ocular Surface Disease Index were measured for period 3 consecutive months participants recruited from clinic-based population at 2 sites. Fifty-two completed (n = 16...
The molecular etiology of human progenitor reprogramming into self-renewing leukemia stem cells (LSC) has remained elusive. Although DNA sequencing uncovered spliceosome gene mutations that promote alternative splicing and portend leukemic transformation, isoform diversity also may be generated by RNA editing mediated adenosine deaminase acting on (ADAR) enzymes regulate cell maintenance. In this study, whole-transcriptome normal, chronic phase, serially transplantable blast crisis myeloid...
Parkinson's disease (PD) and dementia with Lewy bodies are common disorders of the aging population characterized by progressive accumulation α-synuclein (α-syn) in central nervous system. Aggregation α-syn into oligomers a ring-like appearance has been proposed to play role toxicity. However, molecular mechanisms potential sequence events involved formation pore-like structures unclear. We utilized computer modeling cell-based studies investigate process oligomerization wild-type A53T...
Accumulation of α‐synuclein resulting in the formation oligomers and protofibrils has been linked to Parkinson's disease Lewy body dementia. In contrast, β‐synuclein (β‐syn), a close homologue, does not aggregate reduces (α‐syn)‐related pathology. Although considerable information is available about conformation α‐syn at initial end stages fibrillation, less known dynamic process conversion how interactions with antiaggregation chaperones such as might occur. Molecular modeling molecular...
Abstract Aggregation of α‐synuclein (α‐syn) is believed to play a critical role in the pathogenesis disorders such as dementia with Lewy bodies and Parkinson’s disease. The function α‐syn remains unclear, although several lines evidence suggest that involved synaptic vesicle trafficking probably via lipid binding. Moreover, interactions cholesterol lipids have been shown be aggregation. In this context, main objective study was determine if statins – synthesis inhibitors might interfere...
Parkinson's disease (PD) is characterized by accumulation of alpha-synuclein (alpha-syn) and degeneration neuronal populations in cortical subcortical regions. Mitochondrial dysfunction has been considered a potential unifying factor the pathogenesis disease. Mutations genes linked to familial forms PD, including SNCA encoding alpha-syn Pten-induced putative kinase 1 (PINK1), have shown disrupt mitochondrial activity. We investigated mechanisms through which mutant Pink1 might function cells...
Abstract Despite novel therapies, relapse of multiple myeloma (MM) is virtually inevitable. Amplification chromosome 1q, which harbors the inflammation-responsive RNA editase adenosine deaminase acting on (ADAR)1 gene, occurs in 30–50% MM patients and portends a poor prognosis. Since adenosine-to-inosine editing has recently emerged as driver cancer progression, genomic amplification combined with inflammatory cytokine activation ADAR1 could stimulate progression therapeutic resistance....