Article
Biochemistry & Molecular Biology
Emanuela Paldino, Vincenza D'angelo, Mariangela Massaro Cenere, Ezia Guatteo, Simone Barattucci, Giorgia Migliorato, Nicola Berretta, Olaf Riess, Giuseppe Sancesario, Nicola Biagio Mercuri, Francesca Romana Fusco
Summary: This study used immunohistochemical studies to investigate neuropathological changes in a rat transgenic model of Parkinson's disease (PD). It found that in the advanced stages of the disease, there was neuronal loss in the dorsolateral part of the striatum, along with a dramatic loss of parvalbumin interneurons. A marked decrease in the neurotrophic factor called glial-derived neurotrophic factor (GDNF) was also observed in the striatum and substantia nigra of these animals. This confirms the involvement of the striatum in PD pathophysiology and the importance of GDNF in maintaining the health of the substantia nigra.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Vignayanandam Ravindernath-Jayashree Muddapu, Karthik Vijayakumar, Keerthiga Ramakrishnan, V. Srinivasa Chakravarthy
Summary: Parkinson's disease is caused by the progressive loss of dopaminergic cells in the substantia nigra pars compacta, possibly linked to metabolic deficiency. L-DOPA treatment for PD may have toxic effects on neurons. A proposed computational model aims to investigate the mechanism behind neurodegeneration and offer insights for therapeutic development.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Bok-Seok Kim, Taeik Jang, Sung-Eun Yoo, Jae Moon Lee, Eunhee Kim
Summary: The impairment of protein clearance mechanisms in dopaminergic neurons leads to the accumulation of alpha-synuclein, contributing to the pathogenesis of Parkinson's disease. Fas-associated factor 1 (FAF1) was found to disrupt alpha-synuclein clearance through the autophagy-lysosome pathway, indicating a novel role as a negative regulator of autophagic alpha-synuclein clearance. This disturbance ultimately leads to alpha-synuclein accumulation and autophagy dysregulation in PD model mice.
Article
Neurosciences
Ziying Yu, Lishuang Huang, Yinyin Xia, Shuqun Cheng, Cantao Yang, Chengzhi Chen, Zhen Zou, Xiaoliang Wang, Xin Tian, Xuejun Jiang, Lixiao Zhou
Summary: Parkinson's disease (PD) is a neurodegenerative disorder in which m6A modification may play a role. By establishing a PD mouse model, researchers found abnormalities in m6A regulators in learning, memory, and motor functions, as well as significant loss of TH+ neurons in the substantia nigra and striatum.
NEUROSCIENCE LETTERS
(2022)
Article
Multidisciplinary Sciences
Esther Gramage, Jorge Saiz, Rosalia Fernandez-Calle, Yasmina B. Martin, Maria Uribarri, Marcel Ferrer-Alcon, Coral Barbas, Gonzalo Herradon
Summary: This study found that overexpression of PTN has a neuroprotective effect in a mouse model of Parkinson's Disease and identified potential lipid-related drug candidates for Parkinson's Disease.
SCIENTIFIC REPORTS
(2022)
Article
Food Science & Technology
Lei Wang, Shengyu Li, Yu Jiang, Zijian Zhao, Yunjiao Shen, Junjie Zhang, Lei Zhao
Summary: Probiotic Lactobacillus plantarum DP189 has a significant protective effect on the dopaminergic neurons in the substantia nigra of Parkinson's disease mice, improving behavioral abilities and increasing neurotransmitter levels.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Clinical Neurology
Tushar Kamath, Evan Z. Macosko
Summary: Parkinson's disease is characterized by the death of dopaminergic neurons in the substantia nigra. Recent advances in genomic profiling have identified specific pathways and genetic variants involved in the susceptibility of dopaminergic neurons in Parkinson's disease. This provides new opportunities for understanding and developing therapies for this complex disorder.
MOVEMENT DISORDERS
(2023)
Article
Biochemistry & Molecular Biology
Merel Dagher, Katie A. Perrotta, Sara A. Erwin, Ayaka Hachisuka, Rahul Iyer, Sotiris C. Masmanidis, Hongyan Yang, Anne M. Andrews
Summary: Targeting neurons with light-driven opsins is a commonly used approach to study cell-specific responses. In this study, the activation of dopamine neurons resulted in the release of dopamine and serotonin in the striatum, suggesting a potential interaction between these two neurotransmitters.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Clinical Neurology
Marta Gonzalez-Sepulveda, Joan Compte, Thais Cuadros, Alba Nicolau, Camille Guillard-Sirieix, Nuria Penuelas, Marina Lorente-Picon, Annabelle Parent, Jordi Romero-Gimenez, Joana M. Cladera-Sastre, Ariadna Laguna, Miquel Vila
Summary: Neurons that accumulate the highest levels of neuromelanin with age are also the most susceptible to degeneration in Parkinson's disease. Using a neuromelanin-producing rat model, Gonzalez-Sepulveda, Compte et al. show that slowing down age-dependent neuromelanin production can help prevent Parkinson's disease-like features.
Article
Cell Biology
Jie Zhao, Manish Kumar, Jeevan Sharma, Zhihai Yuan
Summary: Arbutin may improve the performance of PD mouse models by inhibiting the function of the A(2A)R and enhancing the effects of cyclic adenosine monophosphate.
NEURAL REGENERATION RESEARCH
(2021)
Article
Neurosciences
Paola Imbriani, Giuseppina Martella, Paola Bonsi, Antonio Pisani
Summary: Parkinson's disease (PD) is a multifactorial disorder with genetic and environmental factors playing a part. Mitochondrial impairment and oxidative stress are important mechanisms in PD, supported by PD-associated genes involved in mitochondrial function. Dysfunction of mitochondria is closely linked to synaptic dysfunction, which is an early event before nigrostriatal neurodegeneration in PD.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Xingxing Jian, Guihu Zhao, He Chen, Yanhui Wang, Jinchen Li, Lu Xie, Bin Li
Summary: This study utilized transcriptomics analysis to identify several hub DEGs between PD patients and normal controls, showing high correlations among these genes. A Cox model with an eight-gene signature was constructed to predict PD progression and survival successfully in an independent dataset, highlighting the clinical significance of these findings.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Liesbeth Reneman, Marieke van der Pluijm, Anouk Schrantee, Elsmarieke van de Giessen
Summary: The dopamine system in the brain plays a crucial role in various neurologic and psychiatric disorders, with PET and SPECT being used to visualize and measure different aspects of the system. New developments in MR imaging offer alternative ways to assess the dopamine system, with techniques like phMRI and NM-MRI showing promise for clinical application.
EUROPEAN JOURNAL OF RADIOLOGY
(2021)
Article
Clinical Neurology
Rahul Gaurav, Lydia Yahia-Cherif, Nadya Pyatigorskaya, Graziella Mangone, Emma Biondetti, Romain Valabregue, Claire Ewenczyk, R. Matthew Hutchison, Jesse M. Cedarbaum, Jean-Christophe Corvol, Marie Vidailhet, Stephane Lehericy
Summary: The study found a progressive decrease in neuromelanin-based substantia nigra signal and volume in PD patients, which could serve as a noninvasive assessment marker for disease progression.
MOVEMENT DISORDERS
(2021)
Article
Neurosciences
Kenan Steidel, Marina C. Ruppert, Andrea Greuel, Masoud Tahmasian, Franziska Maier, Jochen Hammes, Thilo van Eimeren, Lars Timmermann, Marc Tittgemeyer, Alexander Drzezga, David J. Pedrosa, Carsten Eggers
Summary: The network perspective of Parkinson's disease (PD) can be observed using a multimodal imaging approach. The study found that PD patients showed decreased metabolism in the midbrain, dopamine depletion in the striatum, and reduced functional connectivity between the striatum and sensorimotor and frontal areas. PD patients also exhibited stronger decline in striatocortical functional connectivity compared to healthy subjects. The severity of PD was correlated with deterioration in motor scores.
NPJ PARKINSONS DISEASE
(2022)
Review
Clinical Neurology
Wolfgang H. Jost, Carsten Buhmann, Joseph Classen, Karla Eggert, Zacharias Kohl, Tiago Outeiro, Lars Tonges, Dirk Woitalla, Heinz Reichmann
Summary: COMT inhibitors have been established for over 20 years in the treatment of motor fluctuations in Parkinson's disease. However, the available inhibitors differ in pharmacokinetics, indication requirements, and side effects, leading to many patients not receiving optimized drug treatment.
Article
Clinical Neurology
Olivier Rascol, Lars Toenges, Tina DeVries, Mark Jaros, Adrian Quartel, David Jacobs
Summary: The study shows that IR/ER amantadine is effective in reducing LID, but the results vary in different doses and trials. However, despite some adverse events, it still has the potential to be an effective medication in the treatment of LID.
PARKINSONISM & RELATED DISORDERS
(2022)
Article
Neurosciences
P. Riedel, I. M. Domachowska, Y. Lee, P. T. Neukam, L. Tonges, S. C. Li, T. Goschke, M. N. Smolka
Summary: The cognitive control dilemma refers to the balance between stability and flexibility in attention, which is believed to be maintained by dopamine. However, there is limited research on this balance in humans.
PSYCHOPHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Eun Hae Kwon, Sabrina Tennagels, Ralf Gold, Klaus Gerwert, Leon Beyer, Lars Toenges
Summary: This paper emphasizes the importance of reliable objective markers for identifying individuals at risk of Parkinson's disease. Advances in biomarker discovery, particularly in the cerebrospinal fluid (CSF), have provided promising preliminary results. Potential biomarkers include alpha-synuclein species, markers of amyloid and tau pathology, neurofilament light chain, lysosomal enzymes, and markers of neuroinflammation. Metabolomics approaches have also offered insights into novel biological pathways. Genetic forms of PD can help identify subgroups suitable for targeted treatments. Further validation studies are needed to determine the most valuable CSF biomarkers or combinations for clinical and research purposes.
Article
Clinical Neurology
Wolfgang H. Jost, Lars Toenges
Summary: In Parkinson's disease, the focus has traditionally been on motor symptoms and dopaminergic therapy. However, the importance of non-motor symptoms has gained recognition, highlighting the need for treatment of non-dopaminergic deficits. Adenosine A (2A) receptor antagonists have been identified as an additional therapy, as they can modulate the striato-thalamo-cortical loops.
FORTSCHRITTE DER NEUROLOGIE PSYCHIATRIE
(2022)
Review
Clinical Neurology
Lars Toenges, Carsten Buhmann, Stephan Klebe, Jochen Klucken, Eun Hae Kwon, Thomas Mueller, David J. Pedrosa, Nils Schroeter, Peter Riederer, Paul Lingor
Summary: The clinical presentation of Parkinson's disease is complex and heterogeneous, making precise classification challenging. Currently, research is focused on investigating tissue- and fluid-based biomarkers to improve the understanding of Parkinson's disease. Blood-based biomarkers have great potential for use in clinical practice if they meet the necessary requirements. In this review, the knowledge on blood-based biomarkers for Parkinson's disease is summarized from both a researcher's and clinician's perspective.
JOURNAL OF NEURAL TRANSMISSION
(2022)
Letter
Clinical Neurology
Jonas Deppe, Natalie Deininger, Paul Lingor, Tobias B. Haack, Bernhard Haslinger, Marcus Deschauer
MOVEMENT DISORDERS
(2022)
Article
Immunology
Sina Bohnacker, Franziska Hartung, Fiona Henkel, Alessandro Quaranta, Johan Kolmert, Alina Priller, Minhaz Ud-Dean, Johanna Giglberger, Luisa M. Kugler, Lisa Pechtold, Sarah Yazici, Antonie Lechner, Johanna Erber, Ulrike Protzer, Paul Lingor, Percy Knolle, Adam M. Chaker, Carsten B. Schmidt-Weber, Craig E. Wheelock, Julia Esser-von Bieren
Summary: SARS-CoV-2 infection leaves an inflammatory imprint in MDM, resulting in aberrant macrophage function and eicosanoid metabolism, leading to long-term immune aberrations in patients recovering from mild COVID-19.
MUCOSAL IMMUNOLOGY
(2022)
Review
Geriatrics & Gerontology
Lars Toenges, Eun Hae Kwon, Stephan Klebe
Summary: The therapy of neurodegenerative diseases is limited to symptom treatment, but disease-modifying therapies and early diagnosis offer hope for new neuroprotective treatments. Monogenetic forms of Parkinson's disease are likely to benefit from disease-modifying therapies, and biomarkers are crucial for diagnosis and monitoring treatment in clinical trials.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Neurosciences
Andreas Wolfgang Wolff, Bernhard Haller, Antonia Franziska Demleitner, Erica Westenberg, Paul Lingor
Summary: The COVID-19 pandemic has had a significant impact on the medical care of patients with Parkinson's disease, leading to worsening symptoms, appointment cancellations, and difficulties in organizing treatments. Physicians offered alternative consultation options, with telephone consultations being the most accepted by patients.
Review
Neurosciences
Tsepo Goerttler, Eun-Hae Kwon, Michael Fleischer, Mark Stettner, Lars Tonges, Stephan Klebe
Summary: The review examines the impact of SARS-CoV-2 and COVID-19 syndrome on Parkinson's disease patients, discussing symptoms, treatment, and the possibility of the virus causing PD. Additionally, it explores the consequences for asymptomatic and non-affected PD patients, as well as the potential connection between COVID syndrome and PD.
Article
Clinical Neurology
Raphael Scherbaum, Andreas Moewius, Judith Oppermann, Johanna Geritz, Clint Hansen, Ralf Gold, Walter Maetzler, Lars Toenges
Summary: This study found that wearable device-based parameters (DBP) can objectively describe gait and balance impairment in Parkinson's disease (PD) and are correlated with clinical scores. PD-MCT significantly improves gait velocity and stride length and has a positive impact on other DBP. Motor complications and fear of falling may influence the response to PD-MCT. The results of this study suggest that a DBP-based assessment can provide more individualized therapy and improve outcomes for PD patients.
JOURNAL OF NEUROLOGY
(2022)
Article
Medicine, General & Internal
A. E. Lang, A. D. Siderowf, E. A. Macklin, W. Poewe, D. J. Brooks, H. H. Fernandez, O. Rascol, N. Giladi, F. Stocchi, C. M. Tanner, R. B. Postuma, D. K. Simon, E. Tolosa, B. Mollenhauer, J. M. Cedarbaum, K. Fraser, J. Xiao, K. C. Evans, D. L. Graham, I Sapir, J. Inra, R. M. Hutchison, M. Yang, T. Fox, S. Budd Haeberlein, T. Dam
Summary: In participants with early Parkinson's disease, the effects of cinpanemab on clinical measures of disease progression and changes in DaT-SPECT imaging did not differ from those of placebo over a 52-week period.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Clinical Neurology
Qiang Chen, Raphael Scherbaum, Ralf Gold, Kalliopi Pitarokoili, Axel Mosig, Samis Zella, Lars Toenges
Summary: A data-driven clustering analysis was conducted to identify three subtypes of Parkinson's disease: early onset mild type, intermediate type, and late-onset severe type. The Parkinson's Disease Questionnaire (PDQ-39), Non-motor Symptom Questionnaire (NMSQuest), and the MDS-UPDRS Part II were found to be crucial factors for differentiating PD subtypes.
JOURNAL OF NEURAL TRANSMISSION
(2023)
Article
Biochemistry & Molecular Biology
Svitlana Rozanova, Julian Uszkoreit, Karin Schork, Bettina Serschnitzki, Martin Eisenacher, Lars Toenges, Katalin Barkovits-Boeddinghaus, Katrin Marcus
Summary: Proteomic studies using mass spectrometry (MS)-based quantification are important for discovering new biomarkers, but the accuracy of the outcomes can be affected by various analytical conditions. Therefore, it is crucial to assess the quality of the acquired data, including raw data, identification, and quantification levels. This study demonstrates the assessment of four independent datasets from cerebrospinal fluid, highlighting the impact of sample processing-based differences on the quality of quantitative data. Additionally, a free and open source quality control tool called MaCProQC is provided for systematic and rapid data comparison.