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. CONCLUSION: 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.
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. CONCLUSION: 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.
Authors: Joseph C Genereux; Song Qu; Minghai Zhou; Lisa M Ryno; Shiyu Wang; Matthew D Shoulders; Randal J Kaufman; Corinne I Lasmézas; Jeffery W Kelly; R Luke Wiseman Journal: EMBO J Date: 2014-10-31 Impact factor: 11.598
Authors: M Del Campo; C R Oliveira; W Scheper; R Zwart; C Korth; A Müller-Schiffmann; G Kostallas; H Biverstal; J Presto; J Johansson; J J Hoozemans; C F Pereira; C E Teunissen Journal: Cell Mol Life Sci Date: 2014-10-22 Impact factor: 9.261
Authors: Valentín Cóppola-Segovia; Clarissa Cavarsan; Flavia G Maia; Anete C Ferraz; Lia S Nakao; Marcelo Ms Lima; Silvio M Zanata Journal: Mol Neurobiol Date: 2016-09-22 Impact factor: 5.590
Authors: Elisabet Barbero-Camps; Anna Fernández; Anna Baulies; Laura Martinez; Jose C Fernández-Checa; Anna Colell Journal: Am J Pathol Date: 2014-05-09 Impact factor: 4.307