Abstract
Parkinson’s disease (PD) is a multifactorial age-related movement disorder in which defects of both mitochondria and the endoplasmic reticulum (ER) have been reported. The unfolded protein response (UPR) has emerged as a key cellular dysfunction associated with the etiology of the disease. The UPR involves a coordinated response initiated in the endoplasmic reticulum that grants the correct folding of proteins. This review gives insights on the ER and its functioning; the UPR signaling cascades; and the link between ER stress, UPR activation, and physiopathology of PD. Thus, post-mortem studies and data obtained by either in vitro and in vivo pharmacological approaches or by genetic modulation of PD causative genes are described. Further, we discuss the relevance and impact of the UPR to sporadic and genetic PD pathology.
Highlights
Parkinson’s disease (PD) is a multifactorial age-related movement disorder in which defects of both mitochondria and the endoplasmic reticulum (ER) have been reported
This review will discuss the role of the ER and the signaling cascades activated by this organelle during ER stress and how this dysfunction could account for the etiology of PD
The systemic delivery of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) to mice triggers an induction of BiP and CHOP protein and mRNA levels [92], while the intracerebral injection of its metabolite MPP+ in rabbit brain leads an activation of ATF6 pathway in SNpc [112]
Summary
The endoplasmic reticulum is a cellular organelle that controls the synthesis, the folding, and the post-transductional modifications of almost one-third of proteins. It is the first compartment of the secretion pathway (ER–Golgi–lysosome) in eukaryotic cells. The ER forms a network of elongated tubules and flattened discs covering a large part of the cytoplasm that extends to the nuclear envelope [1,2]. Considering the key role of this organelle in the development of the unfolded protein response (UPR), we provide a short description of its structure and functions below
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