A5058385646- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Epigenetics and DNA Methylation
- Nerve injury and regeneration
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetic Neurodegenerative Diseases
- Circadian rhythm and melatonin
- Mitochondrial Function and Pathology
- Neurological disorders and treatments
- HIV Research and Treatment
- Neurogenesis and neuroplasticity mechanisms
- Bioinformatics and Genomic Networks
- Nuclear Receptors and Signaling
- Neurobiology and Insect Physiology Research
- Neuroscience and Neuropharmacology Research
- Olfactory and Sensory Function Studies
- Neurological diseases and metabolism
- RNA regulation and disease
- Stress Responses and Cortisol
- Genetics and Neurodevelopmental Disorders
- Tryptophan and brain disorders
- Dietary Effects on Health
- Dementia and Cognitive Impairment Research
- Neurological Disorders and Treatments
- Ubiquitin and proteasome pathways
University of California, San Diego
2016-2025
Scripps Research Institute
2006-2020
Center for Neurosciences
2011-2016
La Jolla Alcohol Research
2013
The University of Melbourne
2013
National Institute of Biomedical Imaging and Bioengineering
2012
Institute on Aging
2012
Consejo Superior de Investigaciones Científicas
2005
Consejo Nacional de Investigaciones Científicas y Técnicas
1998
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...
The aggregation of proteins into oligomers and amyloid fibrils is characteristic several neurodegenerative diseases, including Parkinson disease (PD). In PD, the process α-synuclein (α-syn) from monomers, via oligomeric intermediates, considered disease-causative toxic mechanism. We developed α-syn mutants that promote oligomer or fibril formation tested toxicity these by using a rat lentivirus system to investigate loss dopaminergic neurons in substantia nigra. most severe nigra observed...
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.
Abnormal deposition and intercellular propagation of α-synuclein plays a central role in the pathogenesis disorders such as Parkinson's Disease (PD) dementia with Lewy bodies (DLB). Previous studies demonstrated that immunization against resulted reduced accumulation synaptic loss transgenic (tg) mouse model, highlighting potential for immunotherapy. However, mechanism by which prevents synucleinopathy-associated deficits remains unknown. Here, we show antibodies specifically target aid...
Parkinson disease (PD) is a multifactorial neurodegenerative disorder with high incidence in the elderly, where environmental and genetic factors are involved etiology. In addition, epigenetic mechanisms, including deregulation of DNA methylation have been recently associated to PD. As accurate diagnosis cannot be achieved pre-mortem, identification early pathological changes crucial enable therapeutic interventions before major neuropathological damage occurs. Here we investigated...
Transcriptional dysregulation has emerged as a core pathologic feature of Huntington's disease (HD), one several triplet-repeat disorders characterized by movement deficits and cognitive dysfunction. Although the mechanisms contributing to gene expression remain unknown, therapeutic strategies have aimed improve transcriptional output via modulation chromatin structure. Recent studies demonstrated effects commercially available histone deacetylase (HDAC) inhibitors in HD models; however,...
DNA methylation is a major epigenetic modification that regulates gene expression. Dnmt1, the maintenance enzyme, abundantly expressed in adult brain and mainly located nuclear compartment, where it has access to chromatin. Hypomethylation of CpG islands at intron 1 SNCA recently been reported result overexpression α-synuclein Parkinson disease (PD) related disorders. We therefore investigated mechanisms underlying altered PD dementia with Lewy bodies (DLB). present evidence reduction Dnmt1...
Circadian disruptions impact nearly all people with Alzheimer's disease (AD), emphasizing both their potential role in pathology and the critical need to investigate therapeutic of circadian-modulating interventions. Here, we show that time-restricted feeding (TRF) without caloric restriction improved key components including behavioral timing, pathology, hippocampal transcription, memory two transgenic (TG) mouse models AD. We found TRF had remarkable capability simultaneously reducing...
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...
<h3>Objective:</h3> We aimed to investigate whether HIV latency in the CNS might have adverse molecular, pathologic, and clinical consequences. <h3>Methods:</h3> This was a case-control comparison of HIV-1 seropositive (HIV+) patients with neuropathologic examination. Based on levels DNA, RNA, p24 brain, cases were classified as controls, latent infection, encephalitis (HIVE). Analysis epigenetic markers including BCL11B, neurodegeneration, neuroinflammation performed utilizing immunoblot,...
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...
Alpha-synuclein (α-Syn) accumulation/aggregation and mitochondrial dysfunction play prominent roles in the pathology of Parkinson's disease. We have previously shown that postmortem human dopaminergic neurons from PD brains accumulate high levels DNA (mtDNA) deletions. now addressed question, whether alterations a component import machinery -TOM40- might contribute to damage PD. For this purpose, we studied TOM40, mtDNA deletions, oxidative damage, energy production, complexes respiratory...
Abnormal accumulation and propagation of the neuronal protein α-synuclein has been hypothesized to underlie pathogenesis Parkinson's disease, dementia with Lewy bodies multiple system atrophy. Here we report a de novo-developed compound (NPT100-18A) that reduces toxicity through novel mechanism involves displacing from membrane. This interacts domain in C-terminus α-synuclein. The E83R mutation interaction 80–90 amino acid region prevents effects NPT100-18A. In vitro studies showed...
Abstract Introduction Circadian alterations are prevalent in Alzheimer's disease (AD) and may contribute to cognitive impairment, behavioral symptoms, neurodegeneration. Epigenetic mechanisms regulate the circadian clock, changes DNA methylation have been reported AD brains, but pathways that mediate deregulation incompletely understood. We hypothesized aberrant affect rhythms AD. Methods investigated methylation, transcription, expression of BMAL1 , a positive regulator cultured fibroblasts...
ABSTRACT The α-proteobacteria phylogenetically related to the Roseobacter clade are predominantly responsible for degradation of organosulfur compounds, including algal osmolyte dimethylsulfoniopropionate (DMSP). Silicibacter sp. strain TM1040, isolated from a DMSP-producing Pfiesteria piscicida dinoflagellate culture, degrades DMSP, producing 3-methylmercaptopropionate. TM1040 possesses three lophotrichous flagella and is highly motile, leading hypothesis that interacts with P. through...
Altered expression and mutations in α-synuclein (α-syn) have been linked to Parkinson's disease (PD) related disorders. The neurological alterations PD patients associated with degeneration of dopaminergic cells other neuronal populations. Moreover, recent studies murine models shown that neurogenesis might also contribute the neurodegenerative phenotype. However, mechanisms involved effects α-syn on are not yet clear. To this end, embryonic stem (mES) were infected lentiviral (LV) vectors...
Abstract We have identified and cataloged 54 genes that exhibit predominant expression in the striatum. Our hypothesis is such mRNA molecules are likely to encode proteins preferentially associated with particular physiological processes intrinsic striatal neurons, therefore might contribute regional specificity of neurodegeneration observed disorders as Huntington's disease (HD). Expression these was measured simultaneously striatum HD R6/1 transgenic mice using Affymetrix oligonucleotide...
Dementia with Lewy bodies (DLB) and Parkinson's Disease (PD) are neurodegenerative disorders of the aging population characterized by abnormal accumulation alpha-synuclein (alpha-syn). Previous studies have suggested that excitotoxicity may contribute to neurodegeneration in these disorders, however underlying mechanisms their relationship alpha-syn remain unclear. For this study we proposed might result alterations metabotropic glutamate receptors (mGluR), particularly mGluR5 which has been...
Parkinson's disease and dementia with Lewy bodies are neurodegenerative disorders characterized by accumulation of α-synuclein (α-syn). Recently, single-chain fragment variables (scFVs) have been developed against individual conformational species α-syn. Unlike more traditional monoclonal antibodies, these scFVs will not activate or be endocytosed Fc receptors. For this study, we investigated an scFV directed oligomeric α-syn fused to the LDL receptor-binding domain from apolipoprotein B...
Parkinson's disease (PD) is a multifactorial where environmental factors act on genetically predisposed individuals. Although only 5% of PD manifestations are associated with specific mutations, majority cases idiopathic origin, environment plays prominent role. Concurrent exposure to Paraquat (PQ) and Maneb (MB) in rural workers increases the risk for adult mice MB/PQ results dopamine fiber loss decreased locomotor activity. While characterized by neuronal substantia nigra, we previously...
Parkinson's Disease (PD) is a common neurodegenerative disorder currently diagnosed based on the presentation of characteristic movement symptoms. Unfortunately, patients exhibiting these symptoms have already undergone significant dopaminergic neuronal loss. Earlier diagnosis, aided by molecular biomarkers specific to PD, would improve overall patient care. Epigenetic mechanisms, which are modified both environment and disease pathophysiology, emerging as important components...