RT journal article
T1 Chaperone proteostasis in Parkinson's disease: stabilization of the Hsp70/alpha-synuclein complex by Hip.
A1 Roodveldt, Cintia
A1 Bertoncini, Carlos
A1 Andersson, August
A1 van der Goot, Annemieke
A1 Hsu, Shang-Te
A1 Fernández-Montesinos, Rafael
A1 de Jong, Jannie
A1 van Ham, Tjakko
A1 Nollen, Ellen
A1 Pozo, David
A1 Christodoulou, John
A1 Dobson, Christopher
A2 Anatomía y Embriología Humana
K1 amyloid
K1 Hip
K1 Hsp70
K1 Parkinson’s disease
K1 synuclein
AB The ATP‐dependent protein chaperone heat‐shock protein 70 (Hsp70) displays broad anti‐aggregation functions and has a critical function in preventing protein misfolding pathologies. According to in vitro and in vivo models of Parkinson's disease (PD), loss of Hsp70 activity is associated with neurodegeneration and the formation of amyloid deposits of α‐synuclein (αSyn), which constitute the intraneuronal inclusions in PD patients known as Lewy bodies. Here, we show that Hsp70 depletion can be a direct result of the presence of aggregation‐prone polypeptides. We show a nucleotide‐dependent interaction between Hsp70 and αSyn, which leads to the aggregation of Hsp70, in the presence of ADP along with αSyn. Such a co‐aggregation phenomenon can be prevented in vitro by the co‐chaperone Hip (ST13), and the hypothesis that it might do so also in vivo is supported by studies of a Caenorhabditis elegans model of αSyn aggregation. Our findings indicate that a decreased expression of Hip could facilitate depletion of Hsp70 by amyloidogenic polypeptides, impairing chaperone proteostasis and stimulating neurodegeneration.
PB Springer
SN 1460-2075
YR 2009
FD 2009-10-29
LK http://hdl.handle.net/10498/38827
UL http://hdl.handle.net/10498/38827
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 06-nov-2026