Mortalin: A Protein Associated With Progression of Parkinson Disease?

Abstract

Parkinson disease (PD) is a progressive neurodegenerative disorder that is considered to affect the brainstem at its early stages and other brain regions, including the limbic system and isocortex, in advanced stages. It has been suggested that PD progression is characterized pathologically by the spreading of Lewy body deposition. To identify novel proteins involved in PD progression, we prepared subcellular fractions from the frontal cortex of pathologically verified PD patients at different stages of disease and Lewy body deposition and from age-matched controls. Protein expression profiles were compared using a robust quantitative proteomic technique called isobaric tagging for relative and absolute quantification in conjunction with mass spectrometry. Approximately 200 proteins were found to display significant differences in their relative abundance between PD patients at various stages and controls. Gene ontology analysis indicated that these altered proteins belonged to many categories (e.g. mitochondrial function and neurotransmission) that were likely critically involved in the pathogenesis of PD. Of those, mortalin, a mitochondrial protein, was decreased in the advanced PD cases and was further validated to be decreased using independent techniques. These results suggest a role for mortalin in PD progression.

Reactivation of protein aggregates by mortalin and Tid1—the human mitochondrial Hsp70 chaperone system

“…Consistent with this role, several studies have shown that mortalin may be implicated in the progression of neurodegenerative and protein aggregation disorders, such as Parkinson and Alzheimer (Burbulla et al 2010;De Mena et al 2009;Deocaris et al 2008;Deocaris et al 2007;Koren et al 2009;Shi et al 2008). Moreover, when mammalian mitochondria are challenged with an imported protein with a strong tendency to form aggregates, the mitochondrial unfolded protein response (mUPR) is activated (Aldridge et al 2007;Zhao et al 2002).…”

Cerebrospinal Fluid Peptides as Potential Parkinson Disease Biomarkers: A Staged Pipeline for Discovery and Validation*

“…Proteomics Data Mining for PD-related Proteins/Peptides-Proteomic data were gathered from our previous quantitative PD-related proteomic studies, including a general human CSF profiling (19), two general human midbrain profiling studies (20,21), general human frontal cortex profiling studies of PD progression (22)(23)(24), glycoprotein profiling studies of human CSF and frontal cortex (25), a phosphoprotein profiling of human frontal cortex (unpublished data), glyco-and phospho-protein profiling studies in a MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model (putamen; unpublished data). A total of 15 data sets were integrated: two on the human CSF proteome, four on the human midbrain (substantia nigra) proteome, six on the human frontal cortex proteome, and the remaining three on the monkey putamen proteome.…”

Down-regulation of Mortalin Exacerbates Aβ-mediated Mitochondrial Fragmentation and Dysfunction

“…Patients-In recent reports, mortalin has been implicated in neurodegenerative diseases, such as Parkinson disease (46,47). However, the implication of mortalin expression with AD has not been elucidated.…”