Assistance for Folding of Disease-Causing Plasma Membrane Proteins.

An extensive catalog of plasma membrane (PM) protein mutations related to phenotypic diseases is associated with incorrect protein folding and/or localization. These impairments, in addition to dysfunction, frequently promote protein aggregation, which can be detrimental to cells. Here, we review PM protein processing, from protein synthesis in the endoplasmic reticulum to delivery to the PM, stressing the main repercussions of processing failures and their physiological consequences in pathologies, and we summarize the recent proposed therapeutic strategies to rescue misassembled proteins through different types of chaperones and/or small molecule drugs that safeguard protein quality control and regulate proteostasis.

Nanodevices that acts as nanocarriers for controlled and directed drug delivery to select cells, organs or tissues in cardiovascular diseases.

Cardiovascular disease, which today represents the main cause of death worldwide, is a likely candidate for the application of nanotechnology in the near future. Nanocarriers are currently being developed to deliver medicine (smart drugs) to selected targets in cells and tissues of blood vessels and the heart, as well as to aid in diagnosis and screening for early detection and individualized treatment. Other applications of nanotechnology hold promise for the long run, such as using nanodevices for drug delivery or correcting the misfolding of proteins. With super-potent effects, nanoparticles should be able to evoke therapeutic effects at a lower dose and for longer periods. The development of nanodevices and nanocarriers must take an integral approach that considers many properties-physical, chemical, biological, biochemical, anatomical, morphological, physiological, pharmacological, toxicological, mechanical, electrical, magnetic, thermodynamic, and optical-in order to evaluate biocompatibility and therefore avoid toxicological and/or other adverse effects. Intensified research in relation to nanocarriers and other nanotechnology could help reduce morbidity and mortality in cardiovascular disease.

Pharmacoperones: targeting therapeutics toward diseases caused by protein misfolding.

Pharmacoperones are hydrophobic molecule drugs that enter cells and serve as a molecular framework to cause misfolded mutant proteins to fold properly and adopt a stable conformation compatible with proper intracellular trafficking. Pharmacoperones have successfully been used experimentally to rescue function of some misfolded proteins (enzymes, receptors, channels) that lead to disease. Identification of pharmacoperones by high-throughput screens of drug libraries will likely provide new molecules that may be potentially useful to treat diseases caused by protein misfolding.