The ER has many complex proteins and so have a robust system for heat-shock protein assisted folding

Furthermore, some heat shock proteins appear to be expressed at higher levels in longer-lived species. The protective nature of many heat shock proteins in experimental models of neurodegeneration supports these hypotheses.

We speculate that the increase in some heat shock proteins in neurodegenerative conditions may be partly responsible for the slow progression of these disorders, whereas the increase in some heat shock proteins with aging may help delay senescence.

Aging is also associated with an accrual of proteotoxic stress and modulates expression of several heat shock proteins. Heat shock protein levels may be increased or decreased in these disorders, with the direction of the response depending on the individual heat shock protein, the disease, cell type, and brain region. These homeostatic functions are especially important in proteinopathic neurodegenerative diseases, in which specific proteins misfold, aggregate, and kill cells through proteotoxic stress.

Some heat shock proteins also directly interfere with apoptosis. Many members of the heat shock protein family act in unison to refold or degrade misfolded proteins.

The ER has many complex proteins and so have a robust system for heat-shock protein assisted folding