Small molecule enhancers of autophagy for neurodegenerative diseases

2008 ◽  
Vol 4 (9) ◽  
pp. 895 ◽  
Author(s):  
Sovan Sarkar ◽  
David C. Rubinsztein
Keyword(s):  
Neurodegenerative Diseases ◽  
Small Molecule ◽  
Small Molecule Enhancers

scholarly journals Prospective discovery of small molecule enhancers of an E3 ligase-substrate interaction

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Kyle R. Simonetta ◽  
Joshua Taygerly ◽  
Kathleen Boyle ◽  
Stephen E. Basham ◽  
Chris Padovani ◽  
...  
Keyword(s):  
Small Molecule ◽  
E3 Ligase ◽  
Substrate Interaction ◽  
Small Molecule Enhancers

scholarly journals Discovery of Small-Molecule Enhancers of Reactive Oxygen Species That are Nontoxic or Cause Genotype-Selective Cell Death

2013 ◽  
Vol 8 (5) ◽  
pp. 923-929 ◽  
Author(s):  
Drew J. Adams ◽  
Zarko V. Boskovic ◽  
Jimmy R. Theriault ◽  
Alex J. Wang ◽  
Andrew M. Stern ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Small Molecule ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Small Molecule Enhancers

scholarly journals Small Molecule Enhancers of Rapamycin-Induced TOR Inhibition Promote Autophagy, Reduce Toxicity in Huntington’s Disease Models and Enhance Killing of Mycobacteria by Macrophages

Autophagy ◽  
2007 ◽  
Vol 3 (6) ◽  
pp. 620-622 ◽  
Author(s):  
R. Andres Floto ◽  
Sovan Sarkar ◽  
Ethan O. Perlstein ◽  
Beate Kampmann ◽  
Stuart L. Schreiber ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Small Molecule ◽  
Disease Models ◽  
Small Molecule Enhancers

Insights into the activity control of the kallikrein-related peptidase 6: small-molecule modulators and allosterism

2018 ◽  
Vol 399 (9) ◽  
pp. 1073-1078 ◽  
Author(s):  
Feryel Soualmia ◽  
Elodie Bosc ◽  
Sabrina Aït Amiri ◽  
Dirk Stratmann ◽  
Viktor Magdolen ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Neurodegenerative Diseases ◽  
Small Molecule ◽  
Serine Proteases ◽  
Short Report ◽  
Small Molecule Modulators ◽  
Suicide Substrates

AbstractThe activity of kallikrein-related peptidase 6 (KLK6) is deregulated in various diseases such as cancer and neurodegenerative diseases. KLK6 is thus considered as an attractive therapeutical target. In this short report, we depict some novel findings on the regulation of the KLK6 activity. Namely, we identified mechanism-based inhibitors (suicide substrates) from an in-house library of 6-substituted coumarin-3-carboxylate derivatives. In addition, a molecular dynamics study evidenced the allosteric behavior of KLK6 similar to that previously observed for some trypsin-like serine proteases. This allosteric behavior together with the coumarinic scaffold bring new opportunities for the design of KLK6 potent activity modulators, useful as therapeutics or activity-based probes.

scholarly journals Small-molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics

2015 ◽  
Vol 112 (31) ◽  
pp. E4281-E4287 ◽  
Author(s):  
Szu-Yu Kuo ◽  
Adam B. Castoreno ◽  
Leslie N. Aldrich ◽  
Kara G. Lassen ◽  
Gautam Goel ◽  
...  
Keyword(s):  
Small Molecule ◽  
Cytokine Production ◽  
Human Genetics ◽  
Diversity Oriented Synthesis ◽  
Inflammatory Cytokine Production ◽  
Disease Phenotypes ◽  
Small Molecule Probes ◽  
Bacterial Replication ◽  
Small Molecule Enhancers

Studies of human genetics and pathophysiology have implicated the regulation of autophagy in inflammation, neurodegeneration, infection, and autoimmunity. These findings have motivated the use of small-molecule probes to study how modulation of autophagy affects disease-associated phenotypes. Here, we describe the discovery of the small-molecule probe BRD5631 that is derived from diversity-oriented synthesis and enhances autophagy through an mTOR-independent pathway. We demonstrate that BRD5631 affects several cellular disease phenotypes previously linked to autophagy, including protein aggregation, cell survival, bacterial replication, and inflammatory cytokine production. BRD5631 can serve as a valuable tool for studying the role of autophagy in the context of cellular homeostasis and disease.

High throughput screening identifies novel, cell cycle-arresting small molecule enhancers of transient protein expression

2017 ◽  
Vol 33 (6) ◽  
pp. 1579-1588 ◽  
Author(s):  
Hermann-Josef Meyer ◽  
Rebecca Turincio ◽  
Shirley Ng ◽  
Juan Li ◽  
Blair Wilson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Expression ◽  
Small Molecule ◽  
High Throughput ◽  
High Throughput Screening ◽  
Transient Protein Expression ◽  
Small Molecule Enhancers

Identification of novel small molecule enhancers of protein production by cultured mammalian cells

2008 ◽  
Vol 100 (6) ◽  
pp. 1193-1204 ◽  
Author(s):  
Martin J. Allen ◽  
James P. Boyce ◽  
Michael T. Trentalange ◽  
David L. Treiber ◽  
Brian Rasmussen ◽  
...  
Keyword(s):  
Small Molecule ◽  
Mammalian Cells ◽  
Protein Production ◽  
Small Molecule Enhancers

scholarly journals Methods to Discover and Evaluate Proteasome Small Molecule Stimulators

Molecules ◽  
2019 ◽  
Vol 24 (12) ◽  
pp. 2341 ◽  
Author(s):  
Rachel A. Coleman ◽  
Darci J. Trader
Keyword(s):  
Neurodegenerative Diseases ◽  
Protein Degradation ◽  
Small Molecule ◽  
Protease Activity ◽  
Ubiquitin Proteasome System ◽  
Proteasome Activity ◽  
Protein Accumulation ◽  
Toxic Protein ◽  
Disease States ◽  
Ubiquitin Proteasome

Protein accumulation has been identified as a characteristic of many degenerative conditions, such as neurodegenerative diseases and aging. In most cases, these conditions also present with diminished protein degradation. The ubiquitin-proteasome system (UPS) is responsible for the degradation of the majority of proteins in cells; however, the activity of the proteasome is reduced in these disease states, contributing to the accumulation of toxic protein. It has been hypothesized that proteasome activity, both ubiquitin-dependent and -independent, can be chemically stimulated to reduce the load of protein in diseased cells. Several methods exist to identify and characterize stimulators of proteasome activity. In this review, we detail the ways in which protease activity can be enhanced and analyze the biochemical and cellular methods of identifying stimulators of both the ubiquitin-dependent and -independent proteasome activities.

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