Publications by authors named "Julie C Necarsulmer"

Article Synopsis
  • TDP-43 proteinopathies, such as frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), are neurodegenerative diseases where the protein TDP-43 misfolds and disrupts neuronal function.
  • Researchers created models that mimic sporadic TDP-43 proteinopathy, showing how acetylation at lysine 145 impairs TDP-43's ability to bind RNA and leads to gene mis-regulation.
  • Results indicate that this acetylation triggers harmful changes in neurons, evidenced by cognitive decline and altered gene expression related to synaptic function, mirroring characteristics seen in human FTLD cases.
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Transactive response DNA-binding protein of 43 kDa (TDP-43) is a highly conserved, ubiquitously expressed nucleic acid-binding protein that regulates DNA/RNA metabolism. Genetics and neuropathology studies have linked TDP-43 to several neuromuscular and neurological disorders including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Under pathological conditions, TDP-43 mislocalizes to the cytoplasm where it forms insoluble, hyper-phosphorylated aggregates during disease progression.

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The orbitofrontal cortex (OFC) is a brain region involved in higher-order decision-making. Rodent studies show that cocaine self-administration (CSA) reduces OFC contribution to goal-directed behavior and behavioral strategies to avoid drug intake. This change in OFC function persists for many weeks after cocaine withdrawal, suggesting involvement in the process of addiction.

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Secreted amyloid precursor protein-alpha (sAPPα), generated by enzymatic processing of the APP, possesses a range of neurotrophic and neuroprotective properties and plays a critical role in the molecular mechanisms of memory and learning. One of the key active regions of sAPPα is the central APP domain (E2) that contains within it the tripeptide sequence, RER. This sequence is exposed on the surface of a coiled coil substructure of E2.

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Eating is a learned process. Our desires for specific foods arise through experience. Both electrical stimulation and optogenetic studies have shown that increased activity in the lateral hypothalamus (LH) promotes feeding.

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Microparticles have potential as neuron-specific delivery platforms and devices with many applications in neuroscience, pharmacology, and biomedicine. To date, most literature suggests that neurons are not phagocytic cells capable of internalizing microparticles larger than 0.5 μm.

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Parkinson's disease is a progressive neurological disorder, marked by the loss of dopaminergic neurons in the nigrostriatal pathway that leads to abnormal gait, rigidity, slowness of movement, and tremor. The ability to recapitulate and measure the neurological sequelae in rodent models of Parkinson's disease is important for studying and evaluating potential therapeutics. Individual variability in lesion severity and injury progression are key factors in the 6-hydroxydopamine model that require normalization when evaluating therapeutic effects.

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