The Aggregation of Huntingtin and α-Synuclein

Abstract

Huntington's and Parkinson's diseases are neurodegenerative disorders associated with unusual protein interactions. Although the origin and evolution of these diseases are completely different, characteristic deposits of protein aggregates (huntingtin and α-synuclein resp.), are a common feature in both diseases. After these observations, many studies are performed with both proteins. Some of them try to understand the nature and driving forces of the aggregation process; others try to find a correlation between the genetic and failure in protein function. Finally with the combination of both approaches, it was proposed that possible strategies deal with pathologic aggregation. Unfortunately, if protein aggregation is a cause or a consequence of the neurodegeneration observed in these pathologies, it is still debatable. This paper describes the process of aggregation of two proteins: huntingtin and α synuclein. The characteristics of the aggregation reaction of these proteins have been followed with novel methods both in vivo and in vitro; these studies include both the combination with other proteins and the presence of various chemical compounds. The ultimate goal of this study was to summarize recent findings on protein aggregation and its possible role as a therapeutic target in neurodegenerative diseases and their role in biomaterial science.

Muscle Histopathological Abnormalities in a Patient With a CCT5 Mutation Predicted to Affect the Apical Domain of the Chaperonin Subunit

“…Consequently, one can expect diverse kinds and levels of failure of protein homeostasis in different cell and tissue types. To further complicate the landscape of deficient protein homeostasis in the whole organism stands the diversity of possible substrates for CCT, which include a variety of proteins: structural ( Yam et al, 2008 ), regulatory of cell cycle and apoptosis ( Willison, 2018a ; 2018b ), and others involved in neural tissue development and degeneration ( Chánez-Cárdenas and Vázquez-Contreras, 2012 ). Substrate selection and binding depend on specific amino acid sequences on the client protein ( Willison, 2018a ; 2018b ) and on the translational context ( Yam et al, 2008 ).…”

Bifunctional Anti-Non-Amyloid Component α-Synuclein Nanobodies Are Protective In Situ

“…Mutant httex1-72Q protein fragments have been shown to form cytoplasmic aggregates and toxicity in vitro in the ST14A cells [13]. In R6/2 and httQ150 transgenic mice brains, with the progression of the disease, the aggregates were shown to become bigger, and functional deficits appeared after the presence of the aggregates [41, 42]. These data indicated the aggregating mhttex1-72Q, as seen in structures referred to here as foci, may be the cause of cellular toxicity in our model.…”

Amyloid Cross-Seeding: Mechanism, Implication, and Inhibition

“…Huntingtin (Htt), a hallmark protein of Huntington’s disease, has been observed to cross-seed and promote the fibrillation of TIA-1, an RNA-binding protein rich in glutamine and asparagine residues [ 202 ]. Another study found the occurrence of polyQ inclusions along with α-syn in samples of brain collected from HD rat models [ 203 , 204 ]. Aβ aggregation was influenced by cross-seeding with unrelated proteins that share a homologous aggregation-prone segment [ 205 ].…”