and progressive dementia, occurring after age 40, associated , as in kuru, with plaques in the brain of affected * Department of Genetics and Howard Hughes Medical Institute individuals (Gerstmann et al., 1936). Multiple affected family members were observed, in a pattern indicating Yale University School of Medicine New Haven, Connecticut 06510 autosomal-dominant inheritance. Similar genetic t...

Prions have served as pathfinders that reveal many aspects of proteostasis in neurons. The recent realization that several prominent neurodegenerative diseases spread via a prion-like mechanism illuminates new possibilities for diagnostics and therapeutics. Thus, key proteins in Alzheimer Disease and Amyotrophic lateral sclerosis (ALS), including amyloid-β precursor protein, Tau and superoxide ...

Transmissible spongiform encephalopathies are characterised by widespread deposition of fibrillar and/or plaque-like forms of the prion protein. These aggregated forms are produced by misfolding of the normal prion protein, PrP(C), to the disease-associated form, PrP(Sc), through mechanisms that remain elusive but which require either direct or indirect interaction between PrP(C) and PrP(Sc) is...

Despite extensive investigation, many features of prion protein misfolding remain enigmatic. Physicochemical variables known to influence misfolding are reviewed to help elucidate the mechanism of prionogenesis and identify salient features of PrP(Sc), the misfolded conformer of the prion protein. Prospective work on refinement of candidate PrP(Sc) models based on thermodynamic considerations w...

Currently, no pharmaceuticals for the etiological treatment of degenerative protein-misfolding diseases (e.g., ALS, Alzheimer's or prion diseases) are commercially available. In this technical note theoretical considerations and practical approaches concerning the development of chaperone-based medications from medicinal plants (e.g., Ginkgo biloba) are reviewed and discussed in detail. Phytoch...

Alzheimer disease (AD) has traditionally been thought to involve the misfolding and aggregation of two different factors that contribute in parallel to pathogenesis: amyloid-β (Aβ) peptides, which represent proteolytic fragments of the transmembrane amyloid precursor protein, and tau, which normally functions as a neuronally enriched, microtubule-associated protein that predominantly accumulate...

Type 2 diabetes (T2D) is a highly prevalent metabolic disease characterized by chronic insulin resistance and β-cell dysfunction and loss, leading to impaired insulin release and hyperglycemia. Although the mechanism responsible for β-cell dysfunction and death is not completely understood, recent findings suggest that the accumulation of misfolded aggregates of the islet amyloid polypeptide (I...