A5075463026- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- RNA Research and Splicing
- Neuroinflammation and Neurodegeneration Mechanisms
- Mitochondrial Function and Pathology
- Nuclear Receptors and Signaling
- Neuroscience and Neural Engineering
- RNA regulation and disease
- Retinal Development and Disorders
- Photoreceptor and optogenetics research
- Neural dynamics and brain function
- Protein Kinase Regulation and GTPase Signaling
- Alzheimer's disease research and treatments
- Genetics and Neurodevelopmental Disorders
- Receptor Mechanisms and Signaling
- Monoclonal and Polyclonal Antibodies Research
- S100 Proteins and Annexins
- Cholinesterase and Neurodegenerative Diseases
- Genetic Neurodegenerative Diseases
- Signaling Pathways in Disease
- Nerve injury and regeneration
- Axon Guidance and Neuronal Signaling
- Anesthesia and Neurotoxicity Research
- Epigenetics and DNA Methylation
- Memory and Neural Mechanisms
Heidelberg University
2016-2025
University of Pittsburgh
2015
Heidelberg University
2011
In-Q-Tel
2011
Center for Neurosciences
2009-2011
Vollum Institute
2009
Institute of Neurobiology
2003-2004
MRC Laboratory of Molecular Biology
1997-2003
Medical Research Council
1997-2001
Harvard University
1991-1995
Calcium ions (Ca 2+ ) act as an intracellular second messenger and can enter neurons through various ion channels. Influx of Ca distinct types channels may differentially activate biochemical processes. N -Methyl-D-aspartate (NMDA) receptors L-type channels, two major sites entry into hippocampal neurons, were found to transmit signals the nucleus regulated gene transcription signaling pathways. Activation multifunctional -calmodulin-dependent protein kinase (CaM kinase) was evoked by...
Mammalian circadian rhythms are regulated by a pacemaker within the suprachiasmatic nuclei (SCN) of hypothalamus. The molecular mechanisms controlling synchronization unknown; however, immediate early gene (IEG) expression in SCN is tightly correlated with entrainment SCN-regulated rhythms. Antibodies were isolated that recognize activated, phosphorylated form transcription factor cyclic adenosine monophosphate response element binding protein (CREB). Within minutes after exposure hamsters...
The N -methyl-D-aspartate (NMDA) receptor, a subtype of glutamate receptors, plays key role in synaptic plasticity the nervous system. After NMDA receptor activation, calcium entry into postsynaptic neuron is critical initial event. However, subsequent mechanisms by which signal processed are incompletely understood. Stimulation cultured rat hippocampal cells with resulted rapid and transient tyrosine phosphorylation 39-kilodalton protein (p39). Tyrosine p39 was triggered required an influx...
Recruitment of the coactivator, CREB binding protein (CBP), by signal-regulated transcription factors, such as [adenosine 3′,5′-monophosphate (cAMP) response element protein], is critical for stimulation gene expression. The mouse pituitary cell line AtT20 was used to show that CBP recruitment step (CREB phosphorylation on serine-133) can be uncoupled from CREB/CBP–activated transcription. found contain a transcriptional activation domain controlled nuclear calcium and...
Synaptic activity can boost neuroprotection through a mechanism that requires synapse-to-nucleus communication and calcium signals in the cell nucleus. Here we show hippocampal neurons nuclear is one of most potent neuronal gene expression. The induction or repression 185 activity-regulated genes dependent upon signaling. calcium-regulated pool contains genomic program mediates synaptic activity-induced, acquired neuroprotection. core set neuroprotective consists 9 principal components,...
Abstract The recent identification of the mitochondrial Ca 2+ uniporter gene (Mcu/Ccdc109a) has enabled us to address its role, and that uptake, in neuronal excitotoxicity. Here we show exogenously expressed Mcu is mitochondrially localized increases levels following NMDA receptor activation, leading increased membrane depolarization excitotoxic cell death. Knockdown endogenous expression reduces NMDA-induced , resulting lower resistance subject dynamic regulation as part an...
Abstract The class II histone deacetylases, HDAC4 and HDAC5, directly bind to repress myogenic transcription factors of the myocyte enhancer factor‐2 (MEF‐2) family thereby inhibiting skeletal myogenesis. During muscle differentiation, repression gene by MEF‐2/HDAC complexes is relieved due calcium/calmodulin‐dependent (CaM) kinase‐induced translocation HDAC5 cytoplasm. MEF‐2 proteins HDACs are also highly expressed in nervous system have been implicated neuronal survival differentiation....
The mechanism by which physiological synaptic NMDA receptor activity promotes neuronal survival is not well understood. Here, we show that an episode of can promote neuroprotection for a long time after has ceased. This long-lasting or “late phase” dependent on nuclear calcium signaling and cAMP response element (CRE)-mediated gene expression. In contrast, evoked acutely ongoing relies solely the activation phosphatidylinositol 3-kinase/Akt pathway. “acute does require independent...
Neuroprotection can be induced by low doses of NMDA, which activate both synaptic and extrasynaptic NMDA receptors. This is in apparent contradiction with our recent findings that receptor signaling exerts a dominant inhibitory effect on prosurvival from Here we report exposure to preconditioning results preferential activation receptors because dramatic increase action potential firing. Both acute long-lasting phases neuroprotection the face apoptotic or excitotoxic insults are dependent...
Mitochondrial Ca2+ overload is a critical, preceding event in neuronal damage encountered during neurodegenerative and ischemic insults. We found that loss of PTEN-induced putative kinase 1 (PINK1) function, implicated Parkinson disease, inhibits the mitochondrial Na+/Ca2+ exchanger (NCLX), leading to impaired extrusion. NCLX activity was, however, fully rescued by activation protein A (PKA) pathway. further show PKA rescues phosphorylating serine 258, regulatory site. Remarkably,...