Current Topics in Medicinal Chemistry - Volume 13, Issue 19, 2013

Prion diseases are a group of fatal neurodegenerative diseases caused by the misfolding of cellular prion protein (PrPC) into pathogenic conformers (PrPSc). Although no effective therapies for prion diseases are currently available, a number of small molecule inhibitors have been identified that are capable of reducing or eliminating PrPSc in prion infected cells. However, recent experiments have shown that upon sustained treat Read More

Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders associated with the conformational conversion of the cellular prion protein, PrPC, into a pathological form known as prion or PrPSc. They can be classified into sporadic, inherited and infectious forms. Spontaneous generation of PrPSc in inherited forms of prion diseases is caused by mutations in the human prion protei Read More

Prion diseases are rare neurodegenerative diseases characterized by the conversion of the prion protein from its native state (PrPC) towards the so-called 'scrapie form', rich in β-strands. Computational approaches, here briefly reviewed, are instrumental to understand the intrinsic instability of PrPC fold and how the latter is affected by mutations, binding of metals as well as by different environmental conditions, such as pH a Read More

A strategy of logical drug design (LDD) and its application to prion diseases are reviewed. LDD is primarily based on the localizability of a hot spot which initiates structural instability in the target protein. It is also based on the regulability of the hot spot by small compounds, their designabilty by a computer, their organic synthesizability and the specificity of their functions once administered to the biological organisms. Unification Read More

Prion diseases, also known as transmissible spongiform encephalopathies (TSEs) are infectious and fatal neurodegenerative diseases. So far, there is no therapy available with clinical efficacy. A detailed survey on the discovery of major classes of small molecule antiprion compounds is documented in this review in the hope that it may shine some light on the future direction of drug discovery against prion and other neu Read More

In the last two decades, knowledge of the neurobiology of prion diseases or transmissible spongiform encephalopathies (TSE) has significantly advanced, but a successful therapy to stop or delay the progression of these disorders remains one of the most challenging goals of biomedical research. Several obstacles to this achievement are in common with other neurodegenerative disorders: difficulties to move from exper Read More

Transmissible spongiform encephalopathies (TSEs), also called prion diseases, are fatal, infectious, genetic or sporadic neurodegenerative disorders of humans and animals. In humans, TSEs are represented by Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome, Fatal Familial Insomnia and Kuru. In animals, the most prominent prion diseases are scrapie of sheep and goats, bovine spongiform encephal Read More

An emerging common feature of the age-associated neurodegenerative disorders like Alzheimer's disease (AD) and Creutzfeldt-Jakob disease (CJD) is the ability of many disease-associated protein aggregates to induce conversion of a normal counterpart conformer leading to an acceleration of disease progression. Curative pharmacotherapy has not been achieved so far despite successes in elucidating pathomechanisms. Here, Read More

Prion diseases are fatal neurodegenerative disorders that affect humans and animals and for which no pharmacological treatment is available. Compounds consisting of two identical moieties joined via an appropriate spacer (i.e. bivalent compounds) have turned out to be effective tools to prevent prion fibril formation and exhibit an improved biological profile with regard to the corresponding monovalent derivatives. In this Read More

Prion diseases belong to a group of fatal infectious diseases with no effective therapies available. Throughout the last 35 years, less than 50 different drugs have been tested in different experimental animal models without hopeful results. An important limitation when searching for new drugs is the existence of appropriate models of the disease. The three different possible origins of prion diseases require the existence o Read More

Prion diseases, or transmissible spongiform encephalopathies, are characterized by abnormal prion protein accumulation in the brain. Abnormal prion proteins, having properties of amyloids when extracted from the brain, are observed as amyloid plaque deposits in the brain in some prion diseases such as variant Creutzfeldt–Jakob disease and Gerstmann–Straussler–Scheinker syndrome. This article reviews amyloid-binding Read More