A5088885335- Alzheimer's disease research and treatments
- RNA regulation and disease
- Prion Diseases and Protein Misfolding
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Parkinson's Disease Mechanisms and Treatments
- Dementia and Cognitive Impairment Research
- Endoplasmic Reticulum Stress and Disease
- Nerve injury and regeneration
- Supramolecular Self-Assembly in Materials
- CRISPR and Genetic Engineering
- Cholinesterase and Neurodegenerative Diseases
- Trace Elements in Health
- Wnt/β-catenin signaling in development and cancer
- Nuclear Receptors and Signaling
Columbia University
2018-2021
University of Minnesota
2012-2018
Columbia University Irving Medical Center
2018
Anna Needs Neuroblastoma Answers
2016
Amid controversy, the cellular form of prion protein PrP c has been proposed to mediate oligomeric amyloid-β (Aβ)-induced deficits. In contrast, there is consistent evidence that Src kinase Fyn activated by Aβ oligomers and leads synaptic cognitive impairment in transgenic animals. However, molecular mechanism which soluble activates remains unknown. Combining use human mouse brain tissue as well primary cortical neurons, we demonstrate binds at neuronal dendritic spines vivo vitro where it...
Oligomeric forms of amyloid-forming proteins are believed to be the principal initiating bioactive species in many neurodegenerative disorders, including Alzheimer's disease (AD). Amyloid-β (Aβ) oligomers implicated AD-associated phosphorylation and aggregation microtubule-associated protein tau. To investigate specific molecular pathways activated by different assemblies, we isolated various Aβ from Tg2576 mice, which a model for AD. We found that Aβ*56, 56-kDa oligomer is detected before...
Mounting evidence indicates that soluble oligomeric forms of amyloid proteins linked to neurodegenerative disorders, such as amyloid-β (Aβ), tau, or α-synuclein (αSyn) might be the major deleterious species for neuronal function in these diseases. Here, we found an abnormal accumulation αSyn AD brains by custom ELISA, size-exclusion chromatography, and nondenaturing/denaturing immunoblotting techniques. Importantly, abundance oligomers human brain tissue correlated with cognitive impairment...
Despite the demonstration that amyloid-β (Aβ) can trigger increased tau phosphorylation and neurofibrillary tangle (NFT) formation in vivo, molecular link associating Aβ pathologies remains ill defined. Here, we observed exposure of cultured primary neurons to trimers isolated from brain tissue subjects with Alzheimer's disease led a specific conformational change detected by antibody Alz50. A similar association was supported postmortem human analyses. To study role created novel bigenic...
Activating Transcription Factor 4 (ATF4) has been postulated as a key regulator of learning and memory. We previously reported that specific hippocampal ATF4 downregulation causes deficits in synaptic plasticity memory reduction glutamatergic functionality. Here we extend our studies to address ATF49s role neuronal excitability. find long-term knockdown cultured rat neurons significantly increases the frequency spontaneous action potentials. This effect is associated with decreased...
Activating transcription factor 4 (ATF4) plays important physiologic roles in the brain including regulation of learning and memory as well neuronal survival death. Yet, outside translational by eIF2α-dependent stress response pathway, there is little information about how its levels are controlled neurons. Here, we show that brain-derived neurotrophic (BDNF) promotes a rapid sustained increase ATF4 transcripts protein levels. This dependent on tropomyosin receptor kinase (TrkB) signaling,...
Abstract Activating transcription factor 4 [ATF4 (also called CREB2)], in addition to its well studied role stress responses, is proposed play important physiologic functions regulating learning and memory. However, the nature of these has not been defined subject apparently disparate views. Here, we provide evidence that ATF4 a regulator excitability during synaptic plasticity. We evaluated mature hippocampal cultures subjected brief chemically induced LTP (cLTP) protocol results changes...
Increasing evidence indicates that plaque-associated amyloid-β (Aβ) oligomers might be responsible for neuronal architecture changes occurring in the vicinity of amyloid deposits Alzheimer's disease. However, underlying mechanism regulating these remains unclear. Cellular prion protein (PrPC) has recently been proposed to act as a receptor Aβ mediates toxicity. We here investigate whether PrPCmediates oligomeric Aβ-induced cytopathology associated with plaques. To understand PrPC...