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Adapting Proteostasis for Disease Intervention
The proteostasis network is described, a set of interacting activities that maintain the health of proteome and the organism that has the potential to ameliorate some of the most challenging diseases of this era.
Opposing Activities Protect Against Age-Onset Proteotoxicity
Because the IIS pathway is central to the regulation of longevity and youthfulness in worms, flies, and mammals, these results suggest a mechanistic link between the aging process and aggregation-mediated proteotoxicity.
Biological and chemical approaches to diseases of proteostasis deficiency.
It is proposed that small molecules can enhance proteostasis by binding to and stabilizing specific proteins (pharmacologic chaperones) or by increasing the protestasis network capacity (proteostasis regulators) and that such therapeutic strategies, including combination therapies, represent a new approach for treating a range of diverse human maladies.
Functional Amyloid Formation within Mammalian Tissue
The discovery of an unprecedented functional mammalian amyloid structure generated by the protein Pmel17 is reported, demonstrating thatAmyloid is a fundamental nonpathological protein fold utilized by organisms from bacteria to humans and mitigating the toxicity associated with melanin formation.
Antibody Domain Exchange Is an Immunological Solution to Carbohydrate Cluster Recognition
The extraordinary configuration of this antibody provides an extended surface, with newly described binding sites, for multivalent interaction with a conserved cluster of oligomannose type sugars on the surface of gp120, finding a previously unappreciated mechanism for high-affinity recognition of carbohydrate or other repeating epitopes on cell or microbial surfaces.
Functional amyloid--from bacteria to humans.
Aβ induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss
The improved eNMDAR antagonist NitroMemantine, which selectively inhibits extrasynaptic over physiological synaptic NMDAR activity, protects synapses from Aβ-induced damage both in vitro and in vivo.