Kaleidoscopic protein-protein interactions in the life and death of ataxin-1: new strategies against protein aggregation

TY - JOUR

T1 - Kaleidoscopic protein-protein interactions in the life and death of ataxin-1

T2 - new strategies against protein aggregation

AU - de Chiara, Cesira

AU - Pastore, Annalisa

PY - 2014/4

Y1 - 2014/4

N2 - Understanding how proteins protect themselves from aberrant aggregation is of primary interest for understanding basic biology, protein biochemistry, and human disease. We discuss the paradigmatic example of ataxin-1 (Atx1), the protein responsible for neurodegenerative spinocerebellar ataxia type 1 (SCA1). This disease is part of the increasing family of pathologies caused by protein aggregation and misfolding. We discuss the importance of protein-protein interactions not only in the nonpathological function of Atx1 but also in protecting the protein from aggregation and misfolding. The lessons learned from Atx1 may lead to a more general understanding of the cell's protective strategies against aggregation. The obtained knowledge may suggest a new perspective for designing specific therapeutic strategies for the cure of misfolding diseases.

AB - Understanding how proteins protect themselves from aberrant aggregation is of primary interest for understanding basic biology, protein biochemistry, and human disease. We discuss the paradigmatic example of ataxin-1 (Atx1), the protein responsible for neurodegenerative spinocerebellar ataxia type 1 (SCA1). This disease is part of the increasing family of pathologies caused by protein aggregation and misfolding. We discuss the importance of protein-protein interactions not only in the nonpathological function of Atx1 but also in protecting the protein from aggregation and misfolding. The lessons learned from Atx1 may lead to a more general understanding of the cell's protective strategies against aggregation. The obtained knowledge may suggest a new perspective for designing specific therapeutic strategies for the cure of misfolding diseases.

KW - misfolding diseases

KW - polyglutamine

KW - protein aggregation

KW - protein-protein interactions

KW - POLYGLUTAMINE DISEASE PROTEIN

KW - SCA1 TRANSGENIC MICE

KW - SPINOCEREBELLAR ATAXIA

KW - AXH DOMAIN

KW - NEURODEGENERATIVE DISEASE

KW - FUNCTIONAL INTERACTIONS

KW - 14-3-3 BINDING

KW - IDENTIFICATION

KW - TYPE-1

KW - GENES

U2 - 10.1016/j.tins.2014.02.003

DO - 10.1016/j.tins.2014.02.003

M3 - Literature review

SN - 0166-2236

VL - 37

SP - 211

EP - 218

JO - Trends in Neurosciences

JF - Trends in Neurosciences

IS - 4

ER -