PD Guide
Protein Misfolding & Aggregation
Protein aggregation is observed in a number of neurodegenerative disorders, including Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease. In PD, misfolded alpha-synuclein is found in aggregates. These protein aggregates are a characteristic clinical feature of PD, though it remains unclear whether protein aggregation is a protective measure or pathogenic mechanism. Dysfunction of molecular chaperones, which ordinarily function to prevent newly synthesized proteins from misfolding and aggregating, has also been hypothesized to play a role in PD.
Responses:
Hsp70 may link parkin ...
Reference:
Auluck PK, Chan EH, Trojanowski JQ, Lee VM, Bonini NM. Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson's disease. Science. 2002;295(5556):865-8.
Luk KC, Mills IP, Trojanowski JQ, Lee VM. Interactions between Hsp70 and the hydrophobic core of alpha-synuclein inhibit fibril assembly. Biochemistry. 2008;47(47):12614-25.
Moore DJ, West AB, Dikeman DA, Dawson VL, Dawson TM. Parkin mediates the degradation-independent ubiquitination of Hsp70. J Neurochem. 2008;105(5):1806-19.