A5035672227- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Nerve injury and regeneration
- Neurological disorders and treatments
- Advanced Nanomaterials in Catalysis
- Supramolecular Self-Assembly in Materials
- Nuclear Receptors and Signaling
- Conducting polymers and applications
- Protein Structure and Dynamics
- Pluripotent Stem Cells Research
- Surface Chemistry and Catalysis
- GABA and Rice Research
- Prion Diseases and Protein Misfolding
- Computational Drug Discovery Methods
- Cancer-related molecular mechanisms research
- Neuroscience and Neural Engineering
- MicroRNA in disease regulation
- CRISPR and Genetic Engineering
- Cellular transport and secretion
- Advanced biosensing and bioanalysis techniques
- Adenosine and Purinergic Signaling
- Iron oxide chemistry and applications
- Electrochemical sensors and biosensors
- Neurological diseases and metabolism
Johns Hopkins Medicine
2016-2025
Johns Hopkins University
2016-2025
Research Network (United States)
2024
Cornell University
2024
Weill Cornell Medicine
2024
Zhengzhou University
2011-2024
Nantong University
2024
Second People's Hospital of NanTong
2024
Children's Hospital of Chongqing Medical University
2021-2023
Australian Regenerative Medicine Institute
2023
INTRODUCTION Parkinson’s disease (PD) is the second most common neurodegenerative disorder and leads to slowness of movement, tremor, rigidity, and, in later stages PD, cognitive impairment. Pathologically, PD characterized by accumulation α-synuclein Lewy bodies neurites. There degeneration neurons throughout nervous system, with dopamine substantia nigra pars compacta leading major symptoms PD. RATIONALE In brains patients, pathologic seems spread from cell via self-amplification,...
PAR promotes α-synuclein toxicity How pathologic (α-syn) leads to neurodegeneration in Parkinson's disease (PD) remains poorly understood. Kam et al. studied the α-syn preformed fibril (α-syn PFF) model of sporadic PD (see Perspective by Brundin and Wyse). They found that α-syn–activated poly(adenosine 5′-diphosphate–ribose) (PAR) polymerase–1 (PARP-1) inhibition PARP or knockout PARP-1 protected mice from pathology. The generation PFF–induced activation converted PFF a strain was 25-fold...
Significance Recent studies have identified a helically folded tetramer as the major normal structure of α-synuclein (α-syn) and that resists aggregation. However, underlying mechanisms regulate formation α-syn tetramers remain elusive. Our study shows mutations in glucocerebrosidase 1 ( GBA1 ) depletion-induced deficiency leading to accumulation glycosphingolipids (GSLs) are sufficient cause destabilization increase susceptibility human dopaminergic neurons cytotoxicity due exposure...
Growing evidence suggests that fine particulate matter (PM
Host anti-viral factors are essential for controlling SARS-CoV-2 infection but remain largely unknown due to the biases of previous large-scale studies toward pro-viral host factors. To fill in this knowledge gap, we perform a genome-wide CRISPR dropout screen and integrate analyses multi-omics data screen, association studies, single-cell RNA-Seq, host-virus proteins or protein/RNA interactome. This study uncovers many that currently underappreciated, including components V-ATPases, ESCRT,...
Visible light (λ > 420 nm) induced photocatalytic degradation of rhodamine B (RhB) in the presence H2O2 by one-dimensional (1D) nanorods goethite (α-FeOOH) and hematite (α-Fe2O3) has been investigated, results were compared to those micrometer-sized rods. α-FeOOH self-assembled oriented attachment primary nanoparticles, while porous α-Fe2O3 rods prepared thermal dehydration respective precursors via a topotactic transformation. The as-prepared samples characterized powder X-ray diffraction,...
Aggregation of α-synuclein contributes to the formation Lewy bodies and neurites, pathologic hallmarks Parkinson disease (PD) α-synucleinopathies. Although a number human mutations have been identified in familial PD, mechanisms that promote accumulation toxicity are poorly understood. Here, we report hyperactivity nonreceptor tyrosine kinase c-Abl critically regulates α-synuclein-induced neuropathology. In mice expressing α-synucleinopathy-associated mutation (hA53Tα-syn mice), deletion...
Background/Aims: Recent studies have shown that circulating microRNAs (miRNAs) are emerging as promising biomarkers for cardiovascular diseases. This study aimed to determine whether miR-19b-3p, miR-134-5p and miR-186-5p can be used novel indicators acute myocardial infarction (AMI). Methods: To investigate the kinetic expression of three selected miRNAs, we enrolled 18 patients with AMI 20 matched controls. Plasma samples were collected from each participant, total RNA was extracted....
Innate immune and inflammatory responses are involved in myocardial ischaemia/reperfusion (I/R) injury. Interleukin (IL)-37 is a newly identified member of the IL-1 family, functions as fundamental inhibitor innate immunity inflammation. However, its role I/R injury remains unknown. or sham operations were performed on male C57BL/6J mice. mice received an injection recombinant human IL-37 vehicle, immediately before reperfusion. Compared with vehicle treatment, treated showed obvious...
Significance The lack of a robust transgenic mouse model loss dopamine (DA) neurons has greatly hindered the study Parkinson’s disease caused by LRRK2 mutations. In this manuscript, we report development catecholaminergic neuron-specific Tet-inducible conditional G2019S and kinase-dead mice, show that LRRK2-induced DA norepinephrine neurodegeneration is kinase-dependent can occur in cell-autonomous manner. Moreover, these models reveal α-synuclein pathology there are defects...
In Parkinson's disease (PD), fibrillar forms of α-synuclein are hypothesized to propagate through synaptically coupled networks, causing Lewy pathology (LP) and neurodegeneration. To more rigorously characterize the determinants spreading, preformed fibrils were injected into mouse pedunculopontine nucleus (PPN), a brain region that manifests LP in PD patients distribution developing compared ascertained by anterograde retrograde connectomic mapping. Within PPN, was cell-specific, being...
The spread of pathological α-synuclein (α-syn) is a crucial event in the progression Parkinson's disease (PD). Cell surface receptors such as lymphocyte activation gene 3 (LAG3) and amyloid precursor-like protein 1 (APLP1) can preferentially bind α-syn over monomeric state to initiate cell-to-cell transmission. However, molecular mechanism underlying this selective binding unknown. Here, we perform an array biophysical experiments reveal that LAG3 D1 APLP1 E1 domains commonly use alkaline...
Pathogenic α-synuclein (α-syn) is a prion-like protein that drives the pathogenesis of Lewy Body Dementia (LBD) and Parkinson's Disease (PD). To target pathogenic α-syn preformed fibrils (PFF), here we designed extracellular disulfide bond-free synthetic nanobody libraries in yeast. Following selection, identified nanobody, PFFNB2, can specifically recognize PFF over monomers. PFFNB2 cannot inhibit aggregation monomer, but significantly dissociate fibrils. Furthermore, adeno-associated virus...
Salt stress has become one major environmental challenge threatening global crop yield. Targeting salt-induced oxidative stress, nanozymes with high-efficiency antioxidant activity and good biocompatibility represent an effective way to improve plant salt tolerance. In this study, carbon dot (CDzymes) derived from glucose histidine are designed alleviate in growth. The CDzymes comprehensively characterized exhibit broad-spectrum capability, allowing them efficiently scavenge reactive oxygen...
Abstract Pathologic α-synuclein (α-syn) spreads from cell-to-cell, in part, through binding to the lymphocyte-activation gene 3 (Lag3). Here we report that amyloid β precursor-like protein 1 (Aplp1) interacts with Lag3 facilitates binding, internalization, transmission, and toxicity of pathologic α-syn. Deletion both Aplp1 eliminates loss dopaminergic neurons accompanying behavioral deficits induced by α-syn preformed fibrils (PFF). Anti-Lag3 prevents internalization PFF disrupting...
Abstract Although the COVID‐19 pandemic has officially ended, persistent challenge of long‐COVID or post‐acute COVID sequelae (PASC) continues to impact societies globally, highlighting urgent need for ongoing research into its mechanisms and therapeutic approaches. Our team recently developed a novel humanized ACE2 mouse model (hACE2ki) designed explicitly long‐COVID/PASC research. This exhibits human expression in tissue cell‐specific patterns akin Ace2. When we exposed young adult hACE2ki...
The bioactive components of goji berries (Lycium barbarum) are crucial determinants their nutritional and commercial value. In this study, we combined hyperspectral imaging technology (HSI) with a one-dimensional convolutional neural network (1DCNN) to predict the content chemical compositions in goji. To enhance model's ability focus on relevant information, introduced channel attention module (CAM), spectral (SAM) fused them together, which can output features convolution kernels...