Abnormal serum concentrations of proteins in Parkinson’s disease

Goldknopf, Ira L.; Bryson, Jennifer; Strelets, Irina; Quintero, Silvia; Sheta, Eman; Mosqueda, Miguel; Park, Helen R.; Appel, Stanley H.; Shill, Holly A.; Sabbagh, Marwan N.; Chase, Bruce A.; Kaldjian, Eric P.; Μarkopoulou, Κaterina

doi:10.1016/j.bbrc.2009.08.150

Cited by 19 publications

(25 citation statements)

References 65 publications

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“…Indeed, this study suggests important hypotheses related to causal mechanisms for testing in experimental models that concern the molecular role of specific 14-3-3 isoforms in the regulation of TPH2, 5-HT, and/or 5-HT 1A receptor binding levels. In addition, the results of this study suggest the possibility that 14-3-3 measurements may serve as an important future method to help identify living infants at risk for SIDS considering that 14-3-3 levels serve as diagnostic biomarkers in the blood and/or cerebrospinal fluid in neurodegenerative disorders in adults (53).…”

Section: Discussionmentioning

confidence: 99%

Brainstem Deficiency of the 14-3-3 Regulator of Serotonin Synthesis: A Proteomics Analysis in the Sudden Infant Death Syndrome

Broadbelt

Rivera

Paterson

et al. 2012

Molecular & Cellular Proteomics

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Impaired brainstem responses to homeostatic challenges during sleep may result in the sudden infant death syndrome (SIDS). Previously we reported a deficiency of serotonin (5-HT) and its key biosynthetic enzyme, tryptophan hydroxylase (TPH2), in SIDS infants in the medullary 5-HT system that modulates homeostatic responses during sleep. Yet, the underlying basis of the TPH2 and 5-HT deficiency is unknown. In this study, we tested the hypothesis that proteomics would uncover previously unrecognized abnormal levels of proteins related to TPH2 and 5-HT regulation in SIDS cases compared with controls, which could provide novel insight into the basis of their deficiency. We first performed a discovery proteomic analysis of the gigantocellularis of the medullary 5-HT system in the same data set with deficiencies of TPH2 and 5-HT levels. Analysis in 6 SIDS cases and 4 controls revealed a 42-75% reduction in abundance in 5 of the 6 isoforms identified of the 14-3-3 signal transduction family, which is known to influence TPH2 activity (p < 0.07). These findings were corroborated in an additional SIDS and control sample using an orthogonal MS E -based quantitative proteomic strategy. To confirm these proteomics results in a larger data set (38 SIDS, 11 controls), we applied Western blot analysis in the gigantocellularis and found that 4/7 14-3-3 isoforms identified were significantly reduced in SIDS cases (p < 0.02), with a 43% reduction in all 14-3-3 isoforms combined (p < 0.001). Abnormalities in 5-HT and TPH2 levels and 5-HT 1A receptor binding were associated with the 14-3-3 deficits in the same SIDS cases. These data suggest a potential molecular defect in SIDS related to TPH2 regulation, as 14-3-3 is critical in this process. Molecular & Cellular Proteomics 11: 10.1074/mcp.M111.009530, 1-17, 2012. The sudden infant death syndrome (SIDS)1 is the sudden unexpected death of an infant less than 1 year of age, with onset of the fatal episode apparently occurring during sleep, that remains unexplained after a thorough investigation, including performance of a complete autopsy and review of the circumstances of death and clinical history (1). It is the leading cause of postneonatal infant mortality in the United States today; with an overall incidence of 0.53/1000 live birth(s) (2). Typically, a seemingly healthy infant is found dead after a sleep period, either in the early morning or after a day-time nap (1,3,4). Impaired brainstem responses to homeostatic challenges during sleep may result in the sleep-related sudden death characteristic of SIDS (4). We have reported various abnormalities in serotonergic (5-HT) receptors, 5-HT transporter, and 5-HT cellular maturation in the medullary 5-HT system in SIDS cases in three independent data sets over the last decade (5-7). This system within the medulla oblongata is a neural network comprised of 5-HT source neurons and their projection sites that help mediate homeostatic responses during the sleep-wake cycle (3). The medullary 5-HT system is defined by us as the regions of t...

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Section: Discussionmentioning

confidence: 99%

Brainstem Deficiency of the 14-3-3 Regulator of Serotonin Synthesis: A Proteomics Analysis in the Sudden Infant Death Syndrome

Broadbelt

Rivera

Paterson

et al. 2012

Molecular & Cellular Proteomics

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“…The majority of associations between AD and albumin is positive, while association with Parkinson's Disease [41][42][43][44] Schizophrenia [45][46][47] and Depression [48][49][50][51][52][53] were mainly negative [40]. Albumin is an acute-phase protein, which can increase or decrease in plasma concentrations as part of an inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Protein Changes in Blood Plasma Associated with the Rate of Cognitive Decline in Alzheimer’s Disease

Sattlecker

Khondoker

Proitsi

et al. 2016

JAD

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Biomarkers of Alzheimer's disease (AD) progression are needed to support the development of urgently needed disease modifying drugs. We employed a SOMAscan assay for quantifying 1,001 proteins in blood samples from 90 AD subjects, 37 stable mild cognitive impaired (MCI) subjects, 39 MCI subjects converting to AD within a year and 69 controls at baseline and one year follow up. We used linear mixed effects models to identify proteins changing significantly over one year with the rate of cognitive decline, which was quantified as the reduction of Mini Mental State Examination (MMSE) scores. Additionally we investigated proteins changing differently across disease groups and during the conversion from MCI to AD. We found that levels of proteins belonging to the complement cascade increase significantly in fast declining AD patients. Longitudinal changes in the complement cascade might be a surrogate biomarker for disease progression. Additionally we found that members of the cytokine-cytokine receptor interaction pathway change during AD when compared to healthy aging subjects.

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“…These candidate markers were then tested in a prospectively collected group of 62 PD patients and 30 controls recruited from two sites. In this validation step, 21 of the candidate proteins contributed significantly to the optimal discrimination between PD and control samples, with a resulting sensitivity of 92.9% and specificity of 93.3% [88]. These 21 putative biomarkers are listed in box 3.…”

Section: Blood Proteomic Findings In Pdmentioning

confidence: 99%

“…One recent systematic analysis of the complete blood serum proteome has brought together a large amount of research into blood-derived proteomic biomarkers for neurodegenerative disease, including PD [88]. These workers first used multivariate discriminate analysis to identify 57 candidate proteins that could discriminate between retrospectively banked serum samples (n = 469) drawn from patients with different diagnoses, including AD, PD and amyotrophic lateral sclerosis.…”

Section: Blood Proteomic Findings In Pdmentioning

confidence: 99%

“…These workers first used multivariate discriminate analysis to identify 57 candidate proteins that could discriminate between retrospectively banked serum samples (n = 469) drawn from patients with different diagnoses, including AD, PD and amyotrophic lateral sclerosis. These proteins were grouped into five classes: cell degeneration biomarkers; haptoglobin proteins; inflammatory proteins; albumin proteins; and unknown proteins [88]. These candidate markers were then tested in a prospectively collected group of 62 PD patients and 30 controls recruited from two sites.…”

Section: Blood Proteomic Findings In Pdmentioning

confidence: 99%

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Exploiting the potential of molecular profiling in Parkinson’s disease: current practice and future probabilities

Mellick

Silburn

Sutherland

et al. 2010

Expert Review of Molecular Diagnostics

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Parkinson's disease (PD) is a common, heterogeneous syndrome diagnosed clinically by the presence of classical neurological symptoms and the absence of 'red flags' that suggest alternative secondary parkinsonian disorders. Neuropathologically, nigrostriatal loss and the presence of proteinaceous inclusions (Lewy bodies) confirm the diagnosis. For PD, molecular profiling promises much but is yet to deliver in terms of breakthroughs for identifying at-risk individuals, detecting disease at early stages, improving diagnostic certainty, prognosticating future outcomes or providing surrogate markers of therapeutic efficacy. Recent, large-scale omics studies, driven by technological advances, have generated terabytes of data but not yet met the goal of developing biomarkers suitable for clinical use in PD. In this article we critically evaluate the recent literature to identify the key roadblocks and realistic opportunities facing researchers interested in utilizing molecular profiling in the clinic to improve the diagnosis and treatment of PD.

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Abnormal serum concentrations of proteins in Parkinson’s disease

Cited by 19 publications

References 65 publications

Brainstem Deficiency of the 14-3-3 Regulator of Serotonin Synthesis: A Proteomics Analysis in the Sudden Infant Death Syndrome

Brainstem Deficiency of the 14-3-3 Regulator of Serotonin Synthesis: A Proteomics Analysis in the Sudden Infant Death Syndrome

Longitudinal Protein Changes in Blood Plasma Associated with the Rate of Cognitive Decline in Alzheimer’s Disease

Exploiting the potential of molecular profiling in Parkinson’s disease: current practice and future probabilities

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