Title:Heat Shock Proteins: Old and Novel Roles in Neurodegenerative Diseases in the Central Nervous System
Volume: 16
Issue: 3
Author(s): Johannes M. van Noort, Marianna Bugiani and Sandra Amor*
Affiliation:
- Department of Pathology, VU University Medical Centre De Boelelaan 1117, 1081 HV Amsterdam,Netherlands
Keywords:
AD, ALS, chaperokines, chaperones, heat shock proteins, immune regulation, MS, neurodegeneration.
Abstract: Heat shock proteins (HSPs) are families of molecular chaperones that play important homeostatic
functions in the central nervous system (CNS) by preventing protein misfolding, promoting degradation
of improperly folded proteins, and protecting against apoptosis and inflammatory damage especially
during hyperthermia, hypoxia, or oxidative stress. Under stress conditions, HSPs are upregulated
to protect cells from damage that accumulates during ageing as well as pathological conditions. An
important, yet frequently overlooked function of some HSPs is their ability to function as extracellular
messengers (also termed chaperokines) that modulate immune responses within the CNS. Given the
strong association between protein aggregation, innate immune cell activation and neurodegeneration,
the expression and roles of HSPs in the CNS is attracting attention in many neurodegenerative disorders
including inflammatory diseases such as multiple sclerosis, protein folding diseases such as Alzheimer’s
disease and amyotrophic lateral sclerosis, and genetic white matter diseases. This is especially so since
several studies show that HSPs act therapeutically by modulating innate immune activation and may
thus serve as neuroprotective agents.
Here we review the evidence linking HSPs with neurodegenerative disorders in humans and the experimental
animal models of these disorders. We discuss the mechanisms by which HSPs protect cells, and
how the knowledge of their endogenous functions can be exploited to treat disorders of the CNS.
