Protein misfolding is the primary cause of several systemic and neurodegenerative diseases and a major challenge in the development of protein-based therapeutics, Figure 1 top. In misfolding diseases such as cystic fibrosis and a1-antitrypsin deficiency, degradation and/or mistrafficking of specific proteins causes loss of protein function. A second class of misfolding disease includes systemic...

Infectious proteins (prions) are usually self-templating filamentous protein polymers (amyloids). Yeast prions are genes composed of protein and, like the multiple alleles of DNA-based genes, can have an array of "variants," each a distinct self-propagating amyloid conformation. Like the lethal mammalian prions and amyloid diseases, yeast prions may be lethal, or only mildly detrimental, and sh...

Liver is one of the most commonly involved organs in both primary and secondary systemic amyloidoses, but hepatic amyloidosis, manifested as mild to moderate enlargement, is usually not symptomatic nor it is clinically problematic. Rarely, massive hepatomegaly, severe cholestatic hepatitis or liver failure may be encountered in patients with systemic amyloidosis. Two cases with lambda light-cha...

Amyloidosis is a disease characterized by deposition of extracellular proteinaceous mate‐ rial known as amyloid in tissues. Amyloidoses are classified according to the protein composition and the clinical characteristics of the disease [1]. Amyloid protein can accu‐ mulate at various speeds in multiple organ systems and the disease can have localized or systemic manifestations depending on orga...

BACKGROUND Cardiac amyloidosis is characterized by amyloid infiltration resulting in extracellular matrix disruption. Amyloid cardiomyopathy due to immunoglobulin light chain protein (AL-CMP) deposition has an accelerated clinical course and a worse prognosis compared with non-light chain cardiac amyloidoses (ie, forms associated with wild-type or mutated transthyretin [TTR]). We therefore test...

Several neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's and prion diseases, are characterized pathognomonically by the presence of intra- and/or extracellular lesions containing proteinaceous aggregates, and by extensive neuronal loss in selective brain regions. Related non-neuropathic systemic diseases, e.g., light-chain and senile systemic amyloidoses, and other o...

The systemic amyloidoses are a group of uncommon diseases characterized by extracellular accumulation of fibrillar proteins, leading to loss of normal tissue architecture and function (1). Light-chain (AL) amyloidosis, which is probably the most frequent form, can potentially involve any organ, but when the heart is affected, the outcome is particularly poor, with a median survival of 4 to 6 mo...

During the past 10 to 15 years, there has been substantial progress in developing new treatments for the systemic amyloidoses. These advances have improved patient outcomes but have also raised new questions with direct clinical implications. For example, development of less intensive treatments for AL amyloidosis has made less certain the role of autologous stem cell transplantation, and new q...