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In Parkinson's disease (PD), dopamine depletion alters neuronal activity in the direct and indirect pathways and leads to increased synchrony in the basal ganglia network. However, the origins of these changes remain elusive. Because GABAergic interneurons regulate activity of projection neurons and promote neuronal synchrony, we recorded from pairs of(More)
Amyotrophic lateral sclerosis (ALS) is a fatal, late-onset neurodegenerative disease primarily affecting motor neurons. A unifying feature of many proteins associated with ALS, including TDP-43 and ataxin-2, is that they localize to stress granules. Unexpectedly, we found that genes that modulate stress granules are strong modifiers of TDP-43 toxicity in(More)
Engineered analog-sensitive (AS) protein kinases have emerged as powerful tools for dissecting phospho-signaling pathways, for elucidating the cellular function of individual kinases, and for deciphering unanticipated effects of clinical therapeutics. A crucial and necessary feature of this technology is a bioorthogonal small molecule that is innocuous(More)
BACKGROUND Although general anesthetics are recognized for their potential to render patients unconscious during surgery, exposure can also lead to long-term outcomes of both cellular damage and protection. As regards the latter, delayed anesthetic preconditioning is an evolutionarily conserved physiological response that has the potential for protecting(More)
Treatment options for people living with amyotrophic lateral sclerosis (ALS) are limited and ineffective. Recently, dexpramipexole (RPPX) was advanced into human ALS clinical trials. In the current studies, we investigated RPPX in two parallel screening systems: 1) appropriately powered, sibling-matched, gender-balanced survival efficacy screening in(More)
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by the progressive deterioration of motor neurons in the cortex and spinal cord. Using an automated robotic microscope platform that enables the longitudinal tracking of thousands of single neurons, we examine the effects a large library of compounds on modulating the(More)
Protein kinase D (PKD) is a novel kinase whose catalytic domain resembles calcium calmodulin kinase and its regulatory domains resemble protein kinase C. We have discovered that (1) PKD is dually regulated by the NMDA and metabotropic glutamate receptors (mGluRs). In turn, PKD regulates AMPAR recycling, especially the GluR2 subunit. (2) We have found that(More)
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