Searching for Potential Lipid Biomarkers of Parkinson’s Disease in Parkin-Mutant Human Skin Fibroblasts by HILIC-ESI-MS/MS: Preliminary Findings

Early diagnosis of neural changes causing cerebral impairment is critical for proposing preventive therapies for Parkinson’s disease (PD). Biomarkers currently available cannot be informative of PD onset since they are characterized by analysing post-mortem tissues from patients with severe degeneration of the substantia nigra. Skin fibroblasts (SF) are now recognized as a useful model of primary human cells, capable of reflecting the chronological and biological aging of the subjects. Here a lipidomic study of easily accessible primary SF is presented, based on hydrophilic interaction liquid chromatography coupled to electrospray ionization and mass spectrometry (HILIC/ESI-MS). Phospholipids (PL) from dermal fibroblasts of five PD patients with different parkin mutations and healthy control SF were characterized by single and tandem MS measurements using a hybrid quadrupole-Orbitrap and a linear ion trap mass analysers. The proposed approach enabled the identification of more than 360 PL. Univariate statistical analyses highlight abnormality of PL metabolism in the PD group, suggesting down- or up-regulation of certain species according to the extent of disease progression. These findings, although preliminary, suggest that the phospholipidome of human SF represents a source of potential biomarkers for the early diagnosis of PD. The dysregulation of ethanolamine plasmalogens in the circulatory system, especially those containing polyunsaturated fatty acids (PUFA), might be likely associated with neurodegeneration.

Download Full-text

Dermal fibroblasts from patients with Parkinson’s disease have normal GCase activity and autophagy compared to patients with PD and GBA mutations

F1000Research ◽

10.12688/f1000research.12090.1 ◽

2017 ◽

Vol 6 ◽

pp. 1751 ◽

Cited By ~ 3

Author(s):

Lucy M Collins ◽

Janelle Drouin-Ouellet ◽

Wei-Li Kuan ◽

Timothy Cox ◽

Roger A Barker

Keyword(s):

Risk Factors ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Genetic Risk ◽

Gaucher Disease ◽

Dermal Fibroblasts ◽

Skin Fibroblasts ◽

Autophagic Flux ◽

Clinical Progression ◽

Gba Mutations

Background: Recently, the development of Parkinson’s disease (PD) has been linked to a number of genetic risk factors, of which the most common is glucocerebrosidase (GBA) mutations. Methods: We investigated PD and Gaucher Disease (GD) patient derived skin fibroblasts using biochemistry assays. Results: PD patient derived skin fibroblasts have normal glucocerebrosidase (GCase) activity, whilst patients with PD and GBA mutations have a selective deficit in GCase enzyme activity and impaired autophagic flux. Conclusions: This data suggests that only PD patients with a GBA mutation have altered GCase activity and autophagy, which may explain their more rapid clinical progression.

Download Full-text

Dermal fibroblasts from patients with Parkinson’s disease have normal GCase activity and autophagy compared to patients with PD and GBA mutations

F1000Research ◽

10.12688/f1000research.12090.2 ◽

2018 ◽

Vol 6 ◽

pp. 1751 ◽

Cited By ~ 3

Author(s):

Lucy M Collins ◽

Janelle Drouin-Ouellet ◽

Wei-Li Kuan ◽

Timothy Cox ◽

Roger A Barker

Keyword(s):

Risk Factors ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Genetic Risk ◽

Gaucher Disease ◽

Dermal Fibroblasts ◽

Skin Fibroblasts ◽

Autophagic Flux ◽

Clinical Progression ◽

Gba Mutations

Download Full-text

Current Therapeutic Strategies and Perspectives for Neuroprotection in Parkinson’s Disease

Current Pharmaceutical Design ◽

10.2174/1381612826666200217114658 ◽

2020 ◽

Vol 26 (37) ◽

pp. 4738-4746

Author(s):

Mohan K. Ghanta ◽

P. Elango ◽

Bhaskar L. V. K. S.

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Early Diagnosis ◽

Neurodegenerative Disorder ◽

Therapeutic Strategies ◽

Neuroprotective Agents ◽

Striatal Neurons ◽

The Status ◽

Advanced Stages ◽

Dopaminergic Pathways

Parkinson’s disease is a progressive neurodegenerative disorder of dopaminergic striatal neurons in basal ganglia. Treatment of Parkinson’s disease (PD) through dopamine replacement strategies may provide improvement in early stages and this treatment response is related to dopaminergic neuronal mass which decreases in advanced stages. This treatment failure was revealed by many studies and levodopa treatment became ineffective or toxic in chronic stages of PD. Early diagnosis and neuroprotective agents may be a suitable approach for the treatment of PD. The essentials required for early diagnosis are biomarkers. Characterising the striatal neurons, understanding the status of dopaminergic pathways in different PD stages may reveal the effects of the drugs used in the treatment. This review updates on characterisation of striatal neurons, electrophysiology of dopaminergic pathways in PD, biomarkers of PD, approaches for success of neuroprotective agents in clinical trials. The literature was collected from the articles in database of PubMed, MedLine and other available literature resources.

Download Full-text

The Role of Salivary Biomarkers in the Early Diagnosis of Alzheimer’s Disease and Parkinson’s Disease

Diagnostics ◽

10.3390/diagnostics11020371 ◽

2021 ◽

Vol 11 (2) ◽

pp. 371

Author(s):

Patrycja Pawlik ◽

Katarzyna Błochowiak

Keyword(s):

Alzheimer’S Disease ◽

Parkinson’S Disease ◽

Alzheimer's Disease ◽

Parkinson's Disease ◽

Early Diagnosis ◽

Neurodegenerative Diseases ◽

Diagnostic Tool ◽

Clinical Symptoms ◽

Early Screening ◽

Salivary Biomarkers

Many neurodegenerative diseases present with progressive neuronal degeneration, which can lead to cognitive and motor impairment. Early screening and diagnosis of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are necessary to begin treatment before the onset of clinical symptoms and slow down the progression of the disease. Biomarkers have shown great potential as a diagnostic tool in the early diagnosis of many diseases, including AD and PD. However, screening for these biomarkers usually includes invasive, complex and expensive methods such as cerebrospinal fluid (CSF) sampling through a lumbar puncture. Researchers are continuously seeking to find a simpler and more reliable diagnostic tool that would be less invasive than CSF sampling. Saliva has been studied as a potential biological fluid that could be used in the diagnosis and early screening of neurodegenerative diseases. This review aims to provide an insight into the current literature concerning salivary biomarkers used in the diagnosis of AD and PD. The most commonly studied salivary biomarkers in AD are β-amyloid1-42/1-40 and TAU protein, as well as α-synuclein and protein deglycase (DJ-1) in PD. Studies continue to be conducted on this subject and researchers are attempting to find correlations between specific biomarkers and early clinical symptoms, which could be key in creating new treatments for patients before the onset of symptoms.

Download Full-text

Early Diagnosis of Parkinson’s Disease in New Neurological Patients by Testing of Visuo-Manual Coordination

Advances in Behavioral Biology - The Basal Ganglia V ◽

10.1007/978-1-4899-0194-1_51 ◽

1996 ◽

pp. 427-431 ◽

Cited By ~ 2

Author(s):

S. Hocherman ◽

N. Giladi

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Early Diagnosis ◽

Neurological Patients

Download Full-text

A Hybrid Extreme Learning Machine Approach for Early Diagnosis of Parkinson’s Disease

Lecture Notes in Computer Science - Advances in Swarm Intelligence ◽

10.1007/978-3-319-11857-4_39 ◽

2014 ◽

pp. 342-349

Author(s):

Yao-Wei Fu ◽

Hui-Ling Chen ◽

Su-Jie Chen ◽

Li-Juan Li ◽

Shan-Shan Huang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Early Diagnosis ◽

Extreme Learning Machine ◽

Learning Machine

Download Full-text

Can Biomarkers Help the Early Diagnosis of Parkinson’s Disease?

Neuroscience Bulletin ◽

10.1007/s12264-017-0174-6 ◽

2017 ◽

Vol 33 (5) ◽

pp. 535-542 ◽

Cited By ~ 17

Author(s):

Weidong Le ◽

Jie Dong ◽

Song Li ◽

Amos D. Korczyn

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Early Diagnosis

Download Full-text

A Simple and Effective Approach Based on a Multi-Level Feature Selection for Automated Parkinson’s Disease Detection

Journal of Personalized Medicine ◽

10.3390/jpm12010055 ◽

2022 ◽

Vol 12 (1) ◽

pp. 55

Author(s):

Fatih Demir ◽

Kamran Siddique ◽

Mohammed Alswaitti ◽

Kursat Demir ◽

Abdulkadir Sengur

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Feature Selection ◽

Early Diagnosis ◽

Neurodegenerative Disorder ◽

Bayesian Optimization ◽

L1 Norm ◽

Bayesian Optimization Algorithm ◽

Knn Classifier ◽

Multi Level

Parkinson’s disease (PD), which is a slowly progressing neurodegenerative disorder, negatively affects people’s daily lives. Early diagnosis is of great importance to minimize the effects of PD. One of the most important symptoms in the early diagnosis of PD disease is the monotony and distortion of speech. Artificial intelligence-based approaches can help specialists and physicians to automatically detect these disorders. In this study, a new and powerful approach based on multi-level feature selection was proposed to detect PD from features containing voice recordings of already-diagnosed cases. At the first level, feature selection was performed with the Chi-square and L1-Norm SVM algorithms (CLS). Then, the features that were extracted from these algorithms were combined to increase the representation power of the samples. At the last level, those samples that were highly distinctive from the combined feature set were selected with feature importance weights using the ReliefF algorithm. In the classification stage, popular classifiers such as KNN, SVM, and DT were used for machine learning, and the best performance was achieved with the KNN classifier. Moreover, the hyperparameters of the KNN classifier were selected with the Bayesian optimization algorithm, and the performance of the proposed approach was further improved. The proposed approach was evaluated using a 10-fold cross-validation technique on a dataset containing PD and normal classes, and a classification accuracy of 95.4% was achieved.

Download Full-text

Age-related pathological impairments in induced neurons derived from patients with idiopathic Parkinson’s disease

10.1101/2021.04.23.441070 ◽

2021 ◽

Author(s):

Janelle Drouin-Ouellet ◽

Karolina Pircs ◽

Emilie M. Legault ◽

Marcella Birtele ◽

Fredrik Nilsson ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Alpha Synuclein ◽

Specific Model ◽

Dermal Fibroblasts ◽

Patient Specific ◽

Idiopathic Parkinson’S Disease ◽

Age Related ◽

Idiopathic Parkinson's Disease ◽

Induced Neurons

AbstractUnderstanding the pathophysiology of Parkinson’s disease has been hampered by the lack of models that recapitulate all the critical factors underlying its development. Here, we generated functional induced dopaminergic neurons (iDANs) that were directly reprogrammed from adult human dermal fibroblasts of patients with idiopathic Parkinson’s disease to investigate diseaserelevant pathology. We show that iDANs derived from Parkinson’s disease patients exhibit lower basal chaperone-mediated autophagy as compared to iDANs of healthy donors. Furthermore, stress-induced autophagy resulted in an accumulation of macroautophagic structures in induced neurons (iNs) derived from Parkinson’s disease patients, independently of the specific neuronal subtype but dependent on the age of the donor. Finally, we found that these impairments in patient-derived iNs lead to an accumulation of phosphorylated alpha-synuclein, a hallmark of Parkinson’s disease pathology. Taken together, our results demonstrate that direct neural reprogramming provides a patient-specific model to study aged neuronal features relevant to idiopathic Parkinson’s disease.

Download Full-text