In the late 1980s, while conducting postgraduate work in the laboratory of biochemist Walter Neupert at the University of Munich, Germany, Hartl collaborated on a series of experiments with Horwich at Yale. Those studies led to the discovery that newly formed cellular proteins fold into their three-dimensional shapes within the barrel-shaped cavity of the so-called chaperonins Hsp60 and GroEL, which are a class of molecular chaperone. Subsequent studies by Hartl, Horwich, and others established details of the chaperone-assisted folding mechanism. At the same time, it became evident that assuming their correct three-dimensional shape not only allows proteins to perform their biological functions, but also prevents them from sticking to other proteins.

Protein misfolding and aggregation are involved in many diseases, including AD, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis (see ARF related news story on Sakahira et al., 2002 and Bonini, 2002 and ARF related news story on Kanekiyo et al., 2007 and Live Discussion). In recent years, several studies have implicated different molecular chaperones, many of which are heat-shock proteins, in neurodegenerative diseases, and found that chaperones' activity decreases with age (Morimoto, 2008). “As each of these diseases exhibits age-dependent effects, the challenge has been to understand how the heat-shock response and chaperone networks become compromised during aging, thus increasing the risk of misfolding diseases,” wrote Morimoto in an e-mail to ARF.—Laura Bonetta.