Activation of the unfolded protein response is an early event in Alzheimer's and Parkinson's disease.
BACKGROUND
Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by the accumulation and aggregation of misfolded proteins. Disturbed homeostasis in the endoplasmic reticulum leads to accumulation of misfolded proteins, which triggers a stress response called the unfolded protein response (UPR) that protects the cell against the toxic buildup of misfolded proteins.


OBJECTIVE
In this paper, we will briefly review the early involvement of the UPR in the pathology of AD and PD.


METHODS
Expression of UPR activation markers was analyzed in human brain tissue using immunohistochemistry and Western blot analysis.


RESULTS
Neuropathological studies demonstrate that UPR activation markers are increased in neurons in AD and PD. In AD, UPR activation markers are observed in neurons with diffuse staining of phosphorylated tau protein. In PD, increased immunoreactivity for UPR activation markers is detected in neuromelanin containing dopaminergic neurons of the substantia nigra, which colocalize with diffuse α-synuclein staining.


CONCLUSIONS
UPR activation is closely associated with the first stages of accumulation and aggregation of the toxic proteins involved in AD and PD. Studies of postmortem brain tissue indicate that UPR activation is an early event in neurodegeneration.
Department of Pathology, VU University Medical Center,  Amsterdam, The Netherlands.
Jeroen J M
JJ
Hoozemans
Elise S
ES
van Haastert
Diana A T
DA
Nijholt
Annemieke J M
AJ
Rozemuller
Wiep
W
Scheper
D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000473:pathology*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure*; D010300:Parkinson Disease / Q000473:pathology* / Q000503:physiopathology; D056811:Unfolded Protein Response / Q000502:physiology*