Preclinical Model to Evaluate Outcomes of Amyloid Cross-Toxicity in the Rodent Brain.

The progress of neurodegenerative disorders correlates with the spread of their associated amyloidogenic proteins. Here, we investigated whether amyloid entry into nonconstitutive neurons could drive cross-toxic outcomes. Amyloid β (Aβ) was stereotaxically introduced into the rodent midbrain tegmentum, where it is not endogenously expressed.

Diseases caused by mutations in the Na/K pump α1 gene .

Human cell survival requires function of the Na/K pump; the heteromeric protein that hydrolyzes ATP to extrude Na and import K across the plasmalemma, thereby building and maintaining these ions' electrochemical gradients. Numerous dominant diseases caused by mutations in genes encoding for Na/K pump catalytic (α) subunit isoforms highlight the importance of this protein. Here, we review literature describing disorders caused by missense mutations in , the gene encoding the ubiquitously expressed α1 isoform of the Na/K pump.

Testing Amyloid Cross-Toxicity in the Vertebrate Brain.

While amyloid proteins such as amyloid β (Aβ),α-synuclein, tau, and lysozyme are known to be prion-like; emerging data have revealed that they are also able to seed the misfolding of prion-like proteins differing in sequence. In the present study, we have developed a tool designed to test neurohistochemical outcomes associated with the entry of an amyloid protein into heterotypic neurons, i.e.

Neuroprotective Effect of Brazilin on Amyloid β (25-35)-Induced Pathology in a Human Neuroblastoma Model.

Until the recent past, the sole exemplar of proteins as infectious agents leading to neurodegenerative disorders remained the prion protein. Since then, the self-seeding mechanism characteristic of the prion protein has also been attributed to other neurodegenerative-disease-associated proteins, including amyloid-β (Aβ), tau, and α-synuclein (α-Syn). In model cell line studies, truncated Aβ, viz.

A Hybrid Model to Study Amyloid Cross-Toxicity.

The self-seeding mechanism characteristic of the prion-protein has also been attributed to other neurodegenerative-disease-associated proteins including amyloid beta (Aβ), tau, and α-synuclein. An interesting facet of these prion-like proteins is their ability to horizontally "spread" and recruit their soluble counterparts in adjacent neurons. However, recent findings suggest a heterotoxic potential in these "seeds" whereby one neurodegeneration-associated protein can interact with another sequentially unrelated prion-like protein and influence its aggregation and drive cross-toxic outcomes and neurodegenerative co-morbidity.

Correction: A new family of fullerene derivatives: fullerene-curcumin conjugates for biological and photovoltaic applications.

[This corrects the article DOI: 10.1039/C8RA08334G.].

A new family of fullerene derivatives: Fullerene-curcumin conjugates for biological and photovoltaic applications.

The synthesis and characterization of a family of [60]fullerocurcuminoids obtained via Bingel reactions is reported. The new C derivatives include curcumin and curcuminoids with a variety of end groups. Preliminary biological experiments show the potential activity of the compound containing a curcumin addend, which exhibits moderate anti-HIV-1 and radical scavenger properties, but no anti-cancer activity.

Looking Back, Looking Forward at Halogen Bonding in Drug Discovery.

Halogen bonding has emerged at the forefront of advances in improving ligand: receptor interactions. In particular the newfound ability of this extant non-covalent-bonding phenomena has revolutionized computational approaches to drug discovery while simultaneously reenergizing synthetic approaches to the field. Here we survey, via examples of classical applications involving halogen atoms in pharmaceutical compounds and their biological hosts, the unique advantages that halogen atoms offer as both Lewis acids and Lewis bases.