• Publications
  • Influence
Parkin Deficiency Increases Vulnerability to Inflammation-Related Nigral Degeneration
TLDR
The studies suggest that loss of Parkin function increases the vulnerability of nigral DA neurons to inflammation-related degeneration, which may enable identification of early biomarkers of degeneration and aid in preclinical screening efforts to identify compounds that can halt or delay the progressive degeneration of the nigrostriatal pathway. Expand
RTA 408, A Novel Synthetic Triterpenoid with Broad Anticancer and Anti-Inflammatory Activity
Semi-synthetic triterpenoids are antioxidant inflammation modulator (AIM) compounds that inhibit tumor cell growth and metastasis. Compounds in the AIM class bind to Keap1 and attenuate Nrf2Expand
Characterization of novel small-molecule NRF2 activators: Structural and biochemical validation of stereospecific KEAP1 binding.
TLDR
This work demonstrates that reversible cyanoenone Michael acceptors, such as the tpAIMs and sA IMs, can be specifically tuned to regulate redox sensitive cysteine residues on key signaling molecules, an approach with significant promise for innovative drug development. Expand
Delayed dominant-negative TNF gene therapy halts progressive loss of nigral dopaminergic neurons in a rat model of Parkinson's disease.
TLDR
These promising findings provide compelling reasons to perform DN-TNF gene transfer studies in nonhuman primates with the long-term goal of using it in the clinic to prevent the delayed and progressive degeneration of DA neurons that gives rise to motor symptoms in PD. Expand
Synthesis, chemical reactivity as Michael acceptors, and biological potency of monocyclic cyanoenones, novel and highly potent anti-inflammatory and cytoprotective agents.
TLDR
In LPS-stimulated macrophages, 1 causes apoptosis and inhibits secretion of TNF-α and IL-1β with potencies that are higher than those of bardoxolone methyl and TBE-31, suggesting that the reactivity of these Michael acceptors is closely related to their biological potency. Expand
Regulation of microglia effector functions by tumor necrosis factor signaling
TLDR
It is found that neither receptor is required to elicit LPS‐evoked TNF production and cytotoxicity on DA cells, and primary microglia deficient in one or both TNF receptors in co‐culture with MN9D cells are employed. Expand
AAV-Dominant Negative Tumor Necrosis Factor (DN-TNF) Gene Transfer to the Striatum Does Not Rescue Medium Spiny Neurons in the YAC128 Mouse Model of Huntington's Disease
TLDR
The extent of striatal DN-TNF gene transfer achieved was not sufficient to achieve robust effects on neuroinflammation, rescue degenerating MSNs or improve motor function in treated mice, and these findings suggest that alternative drug delivery strategies should be explored to determine whether greater target coverage by DN- TNF protein might afford some level of neuroprotection against HD-like pathology. Expand
Cancer Cell Growth Is Differentially Affected by Constitutive Activation of NRF2 by KEAP1 Deletion and Pharmacological Activation of NRF2 by the Synthetic Triterpenoid, RTA 405
TLDR
Assessment of basal levels of KEAP1 and NRF2 in a panel of human tumor cell lines and the activity of an AIM demonstrate that pharmacological activation ofNRF2 by AIMs is distinct from genetic activation and does not provide a growth or survival advantage to tumor cells. Expand
The synthetic triterpenoid, RTA405, increases glomerular filtration rate and reduces angiotensin II-induced contraction of glomerular mesangial cells
TLDR
Nrf2-targeted gene transcription in mesangial cells was associated with decreased basal and reduced angiotensin II-stimulated hydrogen peroxide and calcium ion levels, which may contribute to the GFR increase that occurs following treatment with RTA 405 in rats and may underlie the effect of bardoxolone methyl on the estimated GFR in patients. Expand
The Neuro-Glial Properties of Adipose-Derived Adult Stromal (ADAS) Cells Are Not Regulated by Notch 1 and Are Not Derived from Neural Crest Lineage
TLDR
Although media formulations optimized for MSCs or NSCs enable expansion of mouse ADAS cells in vitro, there is no evidence that these cells are of neural crest origin, that they can undergo robust terminal differentiation into functionally mature neurons, and that Notch 1 is likely to be a key regulator of their cellular and molecular characteristics. Expand
...
1
2
...