A5072285544- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Prion Diseases and Protein Misfolding
- Nuclear Receptors and Signaling
- Peroxisome Proliferator-Activated Receptors
- Adipose Tissue and Metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- Cholinesterase and Neurodegenerative Diseases
- MicroRNA in disease regulation
- Lysosomal Storage Disorders Research
- Computational Drug Discovery Methods
- Neurological disorders and treatments
- Circular RNAs in diseases
- Counseling Practices and Supervision
- Psychiatric care and mental health services
- Genetic Neurodegenerative Diseases
- Retinoids in leukemia and cellular processes
- Neurogenesis and neuroplasticity mechanisms
- Psychotherapy Techniques and Applications
- Calcium signaling and nucleotide metabolism
- Gene Regulatory Network Analysis
- Adenosine and Purinergic Signaling
- Hepatitis C virus research
- Neuroscience and Neural Engineering
- Protein purification and stability
Brigham and Women's Hospital
2017-2023
Harvard University
2017-2023
Exicure (United States)
2020
Rush University Medical Center
2012-2018
Rush University
2013
University of North Dakota
2011
Progressive cerebral accumulation of tau aggregates is a defining feature Alzheimer’s disease (AD). A popular theory that seeks to explain the apparent spread neurofibrillary tangle pathology proposes aggregated passed from neuron neuron. Such templated seeding process requires transferred contains microtubule binding repeat domains are necessary for aggregation. While it not clear how protein such as can move cell cell, previous reports have suggested this may involve extracellular vesicles...
Peroxisome proliferator-activated receptor α (PPARα) is a transcription factor that regulates genes involved in fatty acid catabolism. Here, we provide evidence PPARα constitutively expressed nuclei of hippocampal neurons and, surprisingly, controls calcium influx and the expression various plasticity-related via direct transcriptional regulation cyclic AMP response element binding (CREB). Accordingly, Pparα-null, but not Pparβ-null, mice are deficient CREB memory-associated proteins have...
Neurodegenerative diseases are an enormous public health problem, affecting tens of millions people worldwide. Nearly all these characterized by oligomerization and fibrillization neuronal proteins, there is great interest in therapeutic targeting aggregates. Here, we show that soluble aggregates α-synuclein tau bind to plate-immobilized PrP vitro on mouse cortical neurons, this binding requires at least one the same N-terminal sites which Aβ bind. Moreover, tau, cause both functional...
Significance Although β-amyloid (Aβ) peptides participate in the pathogenesis of Alzheimer’s disease (AD), mechanisms that regulate Aβ production are poorly understood. Here, we demonstrate activation nuclear receptor peroxisome proliferator-activated α (PPARα) upregulates transcription “a disintegrin and metalloproteinase” 10 ( Adam10 ) gene shifts APP processing toward α-secretase pathway. These findings suggest PPARα could be a therapeutic target for reducing burden AD.
Induction of TLR2 activation depends on its association with the adapter protein MyD88. We have found that and MyD88 levels are elevated in hippocampus cortex patients Alzheimer's disease (AD) a 5XFAD mouse model AD. Since there is no specific inhibitor TLR2, to target induced from therapeutic angle, we engineered peptide corresponding TLR2-interacting domain (TIDM) binds BB loop only not other TLRs. Interestingly, WT TIDM inhibited microglial by fibrillar Aβ1-42 lipoteichoic acid, but...
Compelling genetic evidence links the amyloid precursor protein (APP) to Alzheimer's disease (AD) and several theories have been advanced explain relationship. A leading hypothesis proposes that a small amphipathic fragment of APP, β-protein (Aβ), self-associates form soluble aggregates impair synaptic network activity. Here, we used most disease-relevant Aβ, isolated from AD brain. Using this material, show synaptotoxic effects Aβ depend on expression APP Aβ-mediated impairment plasticity...
Intracellular neurofibrillary tangles (NFTs) composed of tau protein are a neuropathological hallmark several neurodegenerative diseases, the most common which is Alzheimer's disease (AD). For some time NFTs were considered primary cause synaptic dysfunction and neuronal death, however, more recent evidence suggests that soluble aggregates key drivers disease. Here we investigated effect different species on plasticity in male rat hippocampus vivo . Intracerebroventricular injection formed...
ABSTRACT The objective of this study was to examine whether altered expression microRNAs in central nervous system components is pathologically linked chronic knee joint pain osteoarthritis. A surgical animal model for OA generated by medial meniscus transection rats followed behavioral tests. Relationships between pathological changes and development were examined histology imaging analyses. Alterations associated with OA-evoked sensation determined bilateral lumbar dorsal root ganglia...
A major challenge for clinical application of pluripotent stem cell therapy Parkinson's disease (PD) is large-scale manufacturing and cryopreservation neurons that can be efficiently prepared with minimal manipulation. To address this obstacle, midbrain dopamine were derived from human induced cells (iPSC-mDA) cryopreserved in large production lots biochemical transplantation studies. Cryopreserved, post-mitotic iPSC-mDA retained high viability gene, protein, electrophysiological signatures...
The early stages of Alzheimer's disease are associated with synaptic dysfunction prior to overt loss neurons. To identify extracellular molecules that impair plasticity in the brain, we studied secretomes human iPSC-derived neuronal models disease. When introduced into rat from neurons either a presenilin-1 mutation, amyloid precursor protein duplication, or trisomy chromosome 21 all strongly inhibit hippocampal long-term potentiation. Synaptic caused by mutant and precusor duplication is...
Immunotherapies targeting extracellular tau share the premise that interrupting cell-to-cell spread of pathology in Alzheimer′s disease (AD) will slow dementia pathogenesis. How these interventions affect actions synaptotoxic, species may help mediate cognitive impairment is relatively unknown. Here, we assayed synaptic plasticity disruption anaesthetised live rats caused by intracerebral injection synaptotoxic present either (a) secretomes induced pluripotent stem cell-derived neurons (iNs)...
Abstract Chronic inflammation is becoming a hallmark of several neurodegenerative disorders and accordingly, IL-1β, proinflammatory cytokine, implicated in the pathogenesis diseases. Although IL-1β binds to its high-affinity receptor, IL-1R, upregulates signaling pathways, IL-1R antagonist (IL-1Ra) adheres same receptor inhibits cell signaling. Therefore, upregulation IL-1Ra considered important attenuating inflammation. The present study underlines novel application gemfibrozil (gem), Food...
Alzheimer's disease (AD) is the most common form of dementia. Despite intense investigations, no effective therapy available to halt its progression. We found that NF-κB was activated within hippocampus and cortex AD subjects forms negatively correlated with cognitive function monitored by Mini-Mental State Examination global z score. Accordingly, activation also observed in a transgenic (5XFAD) mouse model AD. It has been shown peptides corresponding essential modifier (NEMO)-binding domain...
The classical late infantile neuronal ceroid lipofuscinosis (LINCLs) is an autosomal recessive disease, where the defective gene <i>Cln2,</i> encoding tripeptidyl-peptidase I (TPP1). At molecular level, LINCL caused by accumulation of autofluorescent storage materials in neurons and other cell types. Currently, there no established treatment for this fatal disease. This study reveals a novel use gemfibrozil fenofibrate, Food Drug Administration-approved lipid-lowering drugs, up-regulating...
Amyloid β protein (Aβ) and tau, the two main proteins implicated in causing Alzheimer's disease (AD), are posited to trigger synaptic dysfunction long before significant loss occurs vulnerable circuits. Whereas soluble Aβ aggregates from AD brain well recognized potent synaptotoxins, less is known about synaptotoxicity of tau or other tauopathy patient brains. Minimally manipulated patient-derived aqueous extracts contain more diffusible native forms these proteins. Here, we explore how...