Cerebrospinal Fluid Levels of Prodynorphin‐Derived Peptides are Decreased in Huntington's Disease

Shweiki, Mhd Rami Al; Oeckl, Patrick; Pachollek, Adrian; Steinacker, Petra; Barschke, Peggy; Halbgebauer, Steffen; Anderl‐Straub, Sarah; Lewerenz, Jan; Ludolph, Albert C.; Landwehrmeyer, G. Bernhard; Otto, Markus

doi:10.1002/mds.28300

Cited by 14 publications

(21 citation statements)

References 30 publications

(33 reference statements)

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“…The biomarker SIM2 is also supposed to serve as a noble target for Down’s Syndrome-related AD 81 . Although the PDYN gene is extensively studied in Huntington’s Disease 82 , its role in AD is yet to be explored. The interacting biomarkers with AD genes in the MTG region are CDK5, GHSR, PLCB1, ITPKB, HOMER3 ( Fig 5B ).…”

Section: Discussionmentioning

confidence: 99%

A Machine Learning Approach to Unmask Novel Gene Signatures and Prediction of Alzheimer’s Disease Within Different Brain Regions

Sharma

Dey

2021

Preprint

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Alzheimers disease (AD) is a progressive neurodegenerative disorder whose aetiology is currently unknown. Although numerous studies have attempted to identify the genetic risk factor(s) of AD, the interpretability and/or the prediction accuracies achieved by these studies remained unsatisfactory, reducing their clinical significance. Here, we employ the ensemble of random-forest and regularized regression model (LASSO) to the AD-associated microarray datasets from four brain regions - Prefrontal cortex, Middle temporal gyrus, Hippocampus, and Entorhinal cortex- to discover novel genetic biomarkers through a machine learning-based feature-selection classification scheme. The proposed scheme unrevealed the most optimum and biologically significant classifiers within each brain region, which achieved by far the highest prediction accuracy of AD in 5-fold cross-validation (99% average). Interestingly, along with the novel and prominent biomarkers including CORO1C, SLC25A46, RAE1, ANKIB1, CRLF3, PDYN, numerous non-coding RNA genes were also observed as discriminator, of which AK057435 and BC037880 are uncharacterized long non-coding RNA genes.

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Section: Discussionmentioning

confidence: 99%

A Machine Learning Approach to Unmask Novel Gene Signatures and Prediction of Alzheimer’s Disease Within Different Brain Regions

Sharma

Dey

2021

Preprint

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“…Al Shweiki et al 18 measured prodynorphin‐derived peptides and NfL in the CSF of patients with HD, matched controls, and patients with other neurodegenerative disorders using liquid chromatography–mass spectrometry for prodynorphin and established immunoassay for NfL. The levels of prodynorphin‐derived peptides in the CSF of patients with HD were smarkedly decreased in comparison with the age‐matched non‐neurodegenerative controls and also significantly decreased in comparison with patients with amyotrophic lateral sclerosis and Alzheimer's disease/mild cognitive impairment.…”

Section: Figmentioning

confidence: 99%

Cerebrospinal Fluid Markers of Medium Spiny Neuron Injury in Huntington's Disease

Bang

Ross

2021

Movement Disorders

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“…Endogenous opioids are a group of peptides that act on opioids receptors and that derive from proteolytic cleavage of three main precursors: proenkephalin (PENK), prodynorphin (PDYN) and pro-opiomelanocortin [7]. Altered levels of CSF PDYN and/or PENK-derived peptides have been reported in Alzheimer's disease (AD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB) and Huntington's disease (HD) [8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

“…Initial evidence from these studies suggested that decreased CSF PDYN and PENK levels may reflect an impairment and/or neurodegeneration of the striatal medium spiny projection neurons (MSNs), which produce both peptides under dopaminergic signaling [9,10]. Moreover, dysfunctions in the PDYN pathway appear to be involved in developing behavioral and sleep disorders in neurodegenerative disease [12].…”

Section: Introductionmentioning

confidence: 99%

“…Using our previously developed liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in multiple reaction monitoring (MRM) mode for the measurement of CSF PDYN-derived peptides [9] and a new assay for PENK-derived peptides, we investigated the profiles of these markers in sCJD, including its molecular subtypes, and studied the possible associations between the neuropeptide levels and those of other biomarkers and clinical variables, such as disease stage and survival.…”

Section: Introductionmentioning

confidence: 99%

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Prodynorphin and Proenkephalin in Cerebrospinal Fluid of Sporadic Creutzfeldt–Jakob Disease

Abu‐Rumeileh

Barschke

Oeckl

et al. 2022

IJMS

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Proenkephalin (PENK) and prodynorphin (PDYN) are endogenous opioid peptides mainly produced in the striatum and, to a lesser extent, in the cerebral cortex. Dysregulated metabolism and altered cerebrospinal fluid (CSF) levels of PENK and PDYN have been described in several neurodegenerative diseases. However, no study to date investigated these peptides in the CSF of sporadic Creutzfeldt–Jakob disease (sCJD). Using liquid chromatography-multiple reaction monitoring mass spectrometry, we evaluated the CSF PDYN- and PENK-derived peptide levels in 25 controls and 63 patients with sCJD belonging to the most prevalent molecular subtypes (MM(V)1, VV2 and MV2K). One of the PENK-derived peptides was significantly decreased in each sCJD subtype compared to the controls without a difference among subtypes. Conversely, PDYN-derived peptides were selectively decreased in the CSF of sCJD MV2K, a subtype with a more widespread overall pathology compared to the sCJD MM(V)1 and the VV2 subtypes, which we confirmed by semiquantitative analysis of cortical and striatal neuronal loss and astrocytosis. In sCJD CSF PENK and PDYN were associated with CSF biomarkers of neurodegeneration but not with clinical variables and showed a poor diagnostic performance. CSF PDYN and PENK-derived peptides had no significant diagnostic and prognostic values in sCJD; however, the distinct marker levels between molecular subtypes might help to better understand the basis of phenotypic heterogeneity determined by divergent neuronal targeting.

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Cerebrospinal Fluid Levels of Prodynorphin‐Derived Peptides are Decreased in Huntington's Disease

Cited by 14 publications

References 30 publications

A Machine Learning Approach to Unmask Novel Gene Signatures and Prediction of Alzheimer’s Disease Within Different Brain Regions

A Machine Learning Approach to Unmask Novel Gene Signatures and Prediction of Alzheimer’s Disease Within Different Brain Regions

Cerebrospinal Fluid Markers of Medium Spiny Neuron Injury in Huntington's Disease

Prodynorphin and Proenkephalin in Cerebrospinal Fluid of Sporadic Creutzfeldt–Jakob Disease

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