Heat shock proteins
Heat shock proteins
Heat-shock proteins (HSPs), or stress proteins, are present in all organisms and in all cells of all organisms. They are highly conserved across species. Selected HSPs, also known as chaperones, play crucial roles in folding/unfolding of proteins, assembly of multiprotein complexes, transport/sorting of proteins into correct subcellular compartments, cell-cycle control and signaling, and protection of cells against stress/apoptosis. More recently, HSPs have been implicated in antigen presentation with the role of chaperoning and transferring antigenic peptides to the class I and class II molecules of the major histocompatibility complexes. In addition, extracellular HSPs can stimulate professional antigen-presenting cells of the immune system, such as macrophages and dendritic cells.
Mammalian HSPs have been classified into four major families according to their molecular size: HSP100, HSP90, HSP70, HSP60, HSP40 and the small HSPs. Each family of HSPs is composed of members expressed either constitutively or regulated inducibly, and/or targeted to different sub-cellular compartments. For example HSP60, HSC70 or HSP90 are constitutively expressed in mammalian cells while others, HSP27 and HSP70, are strongly induced by different stresses, such as heat, oxidative stress, or anticancer drugs. Recently, it has been recognized that HSPs also regulate apoptosis. HSP27 and HSP70 are antiapoptotic, while HSP60 and HSP10 are proapoptotic.
The transcription factor HSF1 initiates the prolific induction of HSP when cells are exposed to protein damage. Increased protein damage during aging may be exacerbated by a declining heat shock response, reduced levels of heat shock proteins (HSPs), and the resultant loss of protein quality control. Age-dependent waning of the heat shock response is a general effect found in neuronal tissues, skeletal and cardiac muscle and liver. Cells lose the capacity to activate the transcriptional pathways leading to HSP synthesis. In neuronal tissues, decline in protein quality control was widely predicted, as the etiology of a number of diseases involve aggregation-prone proteins that form inclusion bodies whose occurrence is linked to pathology. These diseases include the most frequent neurodegenerative disorder, Alzheimer's disease, an ailment whose pathological symptoms are linked to accumulation of at least two types of inclusion formed from aggregation of the amyloid-β peptide and the cytoskeletal protein tau.