查看文章

Filamentous inclusions of the protein tau in neuronal and glial cells characterize neurodegenerative tauopathies, such as Alzheimer’s disease (AD). The presence of these tau aggregates implies a dysfunction in the chaperone system, the cellular machinery responsible for preventing abnormal accumulation of misfolded proteins. One family of chaperone proteins, heat-shock proteins (HSPs), are synthesized at higher levels in response to cellular stress, and are capable of preventing and repairing protein damage. A promising therapeutic target, these HSPs are among the most potent suppressors of neurodegeneration in animal models, as their upregulation has been shown to prevent and even reverse disease pathology. Why then are endogenous chaperones unable to prevent the protein malfunction and aggregation that characterizes these disorders? Evidence suggests that an age-dependent decline and/or …